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Journal articles on the topic 'Virus-induced enzymes'
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1
Knobil, Katharine, Augustine M. K. Choi, Gordon W. Weigand, and David B. Jacoby. "Role of oxidants in influenza virus-induced gene expression." American Journal of Physiology-Lung Cellular and Molecular Physiology 274, no. 1 (January 1, 1998): L134—L142. http://dx.doi.org/10.1152/ajplung.1998.274.1.l134.
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Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of antioxidant enzymes and in the activation of nuclear factor-κB (NF-κB), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Influenza virus infection also activated NF-κB binding as determined by an electrophoretic mobility shift assay. Pretreatment of A549 cells with N-acetyl-l-cysteine attenuated virus-induced NF-κB activation and interleukin (IL)-8 mRNA induction but did not block induction of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked activation of NF-κB and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induced cell death. Thus oxidants are involved in influenza virus-induced activation of NF-κB, in the expression of IL-8 and MnSOD, and in virus-induced cell death.
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Seo, Young-Jin, Celeste Blake, Stephen Alexander, and Bumsuk Hahm. "Sphingosine 1-Phosphate-Metabolizing Enzymes Control Influenza Virus Propagation and Viral Cytopathogenicity." Journal of Virology 84, no. 16 (June 2, 2010): 8124–31. http://dx.doi.org/10.1128/jvi.00510-10.
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ABSTRACT Sphingosine 1-phosphate (S1P)-metabolizing enzymes regulate the level of sphingolipids and have important biological functions. However, the effects of S1P-metabolizing enzymes on host defense against invading viruses remain unknown. In this study, we investigated the role of S1P-metabolizing enzymes in modulating cellular responses to influenza virus infection. Overexpression of S1P lyase (SPL), which induces the degradation of S1P, interfered with the amplification of infectious influenza virus. Accordingly, SPL-overexpressing cells were much more resistant than control cells to the cytopathic effects caused by influenza virus infection. SPL-mediated inhibition of virus-induced cell death was supported by impairment of the upregulation of the proapoptotic protein Bax, a critical factor for influenza virus cytopathogenicity. Importantly, influenza virus infection of SPL-overexpressing cells induced rapid activation of extracellular signal-regulated kinase (ERK) and STAT1 but not of p38 mitogen-activated protein kinase (MAPK), Akt, or c-Jun N-terminal kinase (JNK). Blockade of STAT1 expression or inhibition of Janus kinase (JAK) activity elevated the level of influenza virus replication in the cells, indicating that SPL protects cells from influenza virus via the activation of JAK/STAT signaling. In contrast to that of SPL, the overexpression of S1P-producing sphingosine kinase 1 heightened the cells' susceptibility to influenza virus infection, an effect that was reversed by the inhibition of its kinase activity, representing opposed enzymatic activity. These findings indicate that the modulation of S1P-metabolizing enzymes is crucial for controlling the host defense against infection with influenza virus. Thus, S1P-metabolizing enzymes are novel potential targets for the treatment of diseases caused by influenza virus infection.
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Bornemann, Claus, and Hartmut Follmann. "Deoxyribonucleotide Synthesis in Phycovirus-Infected Green Algae. A New Virus-Induced Ribonucleotide Reductase." Zeitschrift für Naturforschung C 48, no. 1-2 (February 1, 1993): 113–18. http://dx.doi.org/10.1515/znc-1993-1-222.
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Infection of Chlorella-like green algae with freshwater phycoviruses is associated with a large and rapid demand for DNA precursors which cannot be met by the algal deoxyribonucleotide-synthesizing enzymes. We have demonstrated in these cells an up to ten-fold increase of the key enzyme, ribonucleotide reductase, 1-2 h post infection. The enzyme activity has been partially enriched from cell extracts. In vitro, it differs from that of uninfected algae in three characteristic parameters, viz. eight-fold higher resistance to millimolar hydroxyurea concentrations, much higher optimum concentration of an allosteric effector nucleotide, thymidine triphosphate, and an unusually low temperature optimum at 20 °C. We conclude that the large DNA phycoviruses, like Herpes and pox viruses, code for their own specific ribonucleotide reductase.
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Martínez-Costas, José, Claudia González-López, Vikram N. Vakharia, and Javier Benavente. "Possible Involvement of the Double-Stranded RNA-Binding Core Protein ςA in the Resistance of Avian Reovirus to Interferon." Journal of Virology 74, no. 3 (February 1, 2000): 1124–31. http://dx.doi.org/10.1128/jvi.74.3.1124-1131.2000.
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ABSTRACT Treatment of primary cultures of chicken embryo fibroblasts with a recombinant chicken alpha/beta interferon (rcIFN) induces an antiviral state that causes a strong inhibition of vaccinia virus and vesicular stomatitis virus replication but has no effect on avian reovirus S1133 replication. The fact that avian reovirus polypeptides are synthesized normally in rcIFN-treated cells prompted us to investigate whether this virus expresses factors that interfere with the activation and/or the activity of the IFN-induced, double-stranded RNA (dsRNA)-dependent enzymes. Our results demonstrate that extracts of avian-reovirus-infected cells, but not those of uninfected cells, are able to relieve the translation-inhibitory activity of dsRNA in reticulocyte lysates, by blocking the activation of the dsRNA-dependent enzymes. In addition, our results show that protein ςA, an S1133 core polypeptide, binds to dsRNA in an irreversible manner and that clearing this protein from extracts of infected cells abolishes their protranslational capacity. Taken together, our results raise the interesting possibility that protein ςA antagonizes the IFN-induced cellular response against avian reovirus by blocking the intracellular activation of enzyme pathways dependent on dsRNA, as has been suggested for several other viral dsRNA-binding proteins.
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Hsiang, Tien-Ying, Chen Zhao, and Robert M. Krug. "Interferon-Induced ISG15 Conjugation Inhibits Influenza A Virus Gene Expression and Replication in Human Cells." Journal of Virology 83, no. 12 (April 8, 2009): 5971–77. http://dx.doi.org/10.1128/jvi.01667-08.
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ABSTRACT The ubiquitin-like ISG15 protein, as well as its conjugating enzymes, is induced by type I interferons (IFNs). Experiments using ISG15 knockout (ISG15−/−) mice established that ISG15 and/or its conjugation inhibits the replication of influenza A virus. However, in contrast to the virus inhibition results for mice, the rates of virus replication in ISG15+/+ and ISG15−/− mouse embryo fibroblasts in tissue culture were similar. Here we focus on human tissue culture cells and on the effect of ISG15 and/or its conjugation on influenza A virus gene expression and replication in such cells. We demonstrate that IFN-induced antiviral activity against influenza A virus in human cells is significantly alleviated by inhibiting ISG15 conjugation using small interfering RNAs directed against ISG15-conjugating enzymes. IFN-induced antiviral activity against influenza A virus protein synthesis was reduced 5- to 20-fold by suppressing ISG15 conjugation. The amounts of the viral proteins that were restored by these siRNA treatments were approximately 40 to 50% of the amounts produced in cells that were not pretreated with IFN. Further, we show that ISG15 conjugation inhibits influenza A virus replication 10- to 20-fold at early times after infection in human cells. These results show that ISG15 conjugation plays a substantial role in the antiviral state induced by IFN in human cells. In contrast, we show that in mouse embryo fibroblasts ISG15 conjugation not only does not affect influenza A virus replication but also does not contribute to the IFN-induced antiviral activity against influenza A virus gene expression.
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Choi, A. M., K. Knobil, S. L. Otterbein, D. A. Eastman, and D. B. Jacoby. "Oxidant stress responses in influenza virus pneumonia: gene expression and transcription factor activation." American Journal of Physiology-Lung Cellular and Molecular Physiology 271, no. 3 (September 1, 1996): L383—L391. http://dx.doi.org/10.1152/ajplung.1996.271.3.l383.
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The pathogenesis of influenza virus infections of the lungs is in part mediated by oxidative stress. Such infections might therefore be expected to induce expression of stress-response genes and genes encoding antioxidant enzymes and to activate transcriptional regulatory proteins. Mice (C57B1/6 and C3H/HeJ) were infected intranasally with influenza virus A/PR/8/34 (H1N1). Expression of the genes encoding the antioxidant enzymes manganese superoxide dismutase (Mn- SOD), indoleamine-2, 3-dioxygenase (IDO), heme oxygenase-1, and glutathione peroxidase were increased in the lungs of virus-infected animals. Cu/ZnSOD and catalase mRNA were not induced by viral infection. Activation of the transcriptional regulatory proteins AP-1, C/EBP, and NF-kappa B (which are known to be affected by oxidant stress) was demonstrated by electrophoretic mobility shift assay after viral infection. In the case of MnSOD, despite increased gene expression enzyme activity was not increased. In contrast, for heme oxygenase-1 both mRNA and activity were increased. C3H/ HeJ and C57B1/6 mice, which are known to have different responses to other types of oxidant stress, also differed in their responses to viral infection. Induction of heme oxygenase-1 expression was greater in C57B1/6 mice than in C3H/ HeJ mice, although inhibiting this enzyme did not alter virus-induced mortality. In contrast, IDO was more strongly induced in C3H/HeJ mice. Activation of NF-kappa B was much more marked in C57B1/6 mice than in C3H/HeJ mice. Although virus replication and inflammatory responses were equivalent in the two strains, lung injury (as measured by wet-to-dry wt ratios) and mortality were greater in C3H/HeJ mice than in C57B1/6 mice, a difference that may be related to differing oxidant stress responses. Thus influenza pneumonia causes an oxidant stress response in the lungs, the nature of which is determined in part by the genetic background of the host.
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Knoester, Marga. "Virus-Induced Gene Expression for Enzymes of Ethylene Biosynthesis in Hypersensitively Reacting Tobacco." Molecular Plant-Microbe Interactions 8, no. 1 (1995): 177. http://dx.doi.org/10.1094/mpmi-8-0177.
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Staley, S., Marcela Smid, Sarah Dotters-Katz, and Elizabeth Stringer. "Epstein–Barr Virus-Induced Mononucleosis as an Imitator of Severe Preeclampsia." American Journal of Perinatology Reports 07, no. 01 (January 2017): e5-e7. http://dx.doi.org/10.1055/s-0036-1597265.
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Background In pregnancy, conditions presenting with hematologic abnormalities, transaminitis, and proteinuria pose diagnostic challenges in pregnancy. Case We present the case of an 18-year-old woman, G1P0, at 33 weeks' gestation with fever of unknown cause, who developed progressively elevated liver enzymes, proteinuria, and thrombocytopenia, due to Epstein–Barr virus (EBV) infection. Conclusion Acute infection with EBV should be included in the differential diagnosis of preeclampsia with severe features, particularly in the setting of fever. Supportive treatment and observation may prevent iatrogenic preterm birth.
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Drecktrah, Daniel, and William J. Brown. "Phospholipase A2Antagonists Inhibit Nocodazole-induced Golgi Ministack Formation: Evidence of an ER Intermediate and Constitutive Cycling." Molecular Biology of the Cell 10, no. 12 (December 1999): 4021–32. http://dx.doi.org/10.1091/mbc.10.12.4021.
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Evidence has been presented both for and against obligate retrograde movement of resident Golgi proteins through the endoplasmic reticulum (ER) during nocodazole-induced Golgi ministack formation. Here, we studied the nocodazole-induced formation of ministacks using phospholipase A2(PLA2) antagonists, which have been shown previously to inhibit brefeldin A–stimulated Golgi-to-ER retrograde transport. Examination of clone 9 rat hepatocytes by immunofluorescence and immunoelectron microscopy revealed that a subset of PLA2antagonists prevented nocodazole-induced ministack formation by inhibiting two different trafficking pathways for resident Golgi enzymes; at 25 μM, retrograde Golgi-to-ER transport was inhibited, whereas at 5 μM, Golgi-to-ER trafficking was permitted, but resident Golgi enzymes accumulated in the ER. Moreover, resident Golgi enzymes gradually redistributed from the juxtanuclear Golgi or Golgi ministacks to the ER in cells treated with these PLA2antagonists alone. Not only was ER-to-Golgi transport of resident Golgi enzymes inhibited in cells treated with these PLA2antagonists, but transport of the vesicular stomatitis virus G protein out of the ER was also prevented. These results support a model of obligate retrograde recycling of Golgi resident enzymes during nocodazole-induced ministack formation and provide additional evidence that resident Golgi enzymes slowly and constitutively cycle between the Golgi and ER.
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Wijekoon, Champa P., and Peter J. Facchini. "Systematic knockdown of morphine pathway enzymes in opium poppy using virus-induced gene silencing." Plant Journal 69, no. 6 (December 28, 2011): 1052–63. http://dx.doi.org/10.1111/j.1365-313x.2011.04855.x.
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Siregar, Gontar Alamsyah, Ginanda Putra Siregar, Darmadi Darmadi, and Riska Habriel Ruslie. "Coronavirus Disease-19 and Liver Injury." Open Access Macedonian Journal of Medical Sciences 8, T1 (September 30, 2020): 154–57. http://dx.doi.org/10.3889/oamjms.2020.5028.
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Coronavirus Disease (COVID)-19 is a pandemic since March 11, 2020. The total case is more than a half million worldwide. Liver injury is quite common in COVID-19 patients. Direct viral infection is possible due to the presence of angiotensin converting enzyme 2 in cholangiocytes and hepatocytes. Other proposed mechanisms are virus-induced cytopathic effects, inflammation process, hypoxia and shock, increased apoptotic activity, increased positive end expiratory effect, and drug-induced. The manifestation of liver injury is mild and transient with elevated liver enzymes, bilirubin, and gamma-glutamyl transferase levels. Deterioration of liver function can occur in subjects with COVID-19 and underlying liver injury. The management is principally supportive. Hepatoprotective drugs may be administered in severe cases.
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Jiang, Dong, Jessica M. Weidner, Min Qing, Xiao-Ben Pan, Haitao Guo, Chunxiao Xu, Xianchao Zhang, et al. "Identification of Five Interferon-Induced Cellular Proteins That Inhibit West Nile Virus and Dengue Virus Infections." Journal of Virology 84, no. 16 (June 9, 2010): 8332–41. http://dx.doi.org/10.1128/jvi.02199-09.
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ABSTRACT Interferons (IFNs) are key mediators of the host innate antiviral immune response. To identify IFN-stimulated genes (ISGs) that instigate an antiviral state against two medically important flaviviruses, West Nile virus (WNV) and dengue virus (DENV), we tested 36 ISGs that are commonly induced by IFN-α for antiviral activity against the two viruses. We discovered that five ISGs efficiently suppressed WNV and/or DENV infection when they were individually expressed in HEK293 cells. Mechanistic analyses revealed that two structurally related cell plasma membrane proteins, IFITM2 and IFITM3, disrupted early steps (entry and/or uncoating) of the viral infection. In contrast, three IFN-induced cellular enzymes, viperin, ISG20, and double-stranded-RNA-activated protein kinase, inhibited steps in viral proteins and/or RNA biosynthesis. Our results thus imply that the antiviral activity of IFN-α is collectively mediated by a panel of ISGs that disrupt multiple steps of the DENV and WNV life cycles.
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Tian, Xiu, Ju-Xin Ruan, Jin-Quan Huang, Chang-Qing Yang, Xin Fang, Zhi-Wen Chen, Hui Hong, et al. "Characterization of gossypol biosynthetic pathway." Proceedings of the National Academy of Sciences 115, no. 23 (May 21, 2018): E5410—E5418. http://dx.doi.org/10.1073/pnas.1805085115.
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Gossypol and related sesquiterpene aldehydes in cotton function as defense compounds but are antinutritional in cottonseed products. By transcriptome comparison and coexpression analyses, we identified 146 candidates linked to gossypol biosynthesis. Analysis of metabolites accumulated in plants subjected to virus-induced gene silencing (VIGS) led to the identification of four enzymes and their supposed substrates. In vitro enzymatic assay and reconstitution in tobacco leaves elucidated a series of oxidative reactions of the gossypol biosynthesis pathway. The four functionally characterized enzymes, together with (+)-δ-cadinene synthase and the P450 involved in 7-hydroxy-(+)-δ-cadinene formation, convert farnesyl diphosphate (FPP) to hemigossypol, with two gaps left that each involves aromatization. Of six intermediates identified from the VIGS-treated leaves, 8-hydroxy-7-keto-δ-cadinene exerted a deleterious effect in dampening plant disease resistance if accumulated. Notably, CYP71BE79, the enzyme responsible for converting this phytotoxic intermediate, exhibited the highest catalytic activity among the five enzymes of the pathway assayed. In addition, despite their dispersed distribution in the cotton genome, all of the enzyme genes identified show a tight correlation of expression. Our data suggest that the enzymatic steps in the gossypol pathway are highly coordinated to ensure efficient substrate conversion.
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Patel, Jenish R., Bradley T. Christoph, Sakina F. Hussain, Keyur P. Vora, Priya Ranjan, Suryaprakash Sambhara, and Shivaprakash Gangappa. "Impact of NADPH Oxidase Inhibition on Influenza A Virus-induced Inflammation (134.80)." Journal of Immunology 182, no. 1_Supplement (April 1, 2009): 134.80. http://dx.doi.org/10.4049/jimmunol.182.supp.134.80.
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Abstract Activation of innate immunity pathways in susceptible cell types is critical for host defense against influenza-A viruses (IAV). Based on studies signifying a role for NOX1 in inflammation, we hypothesized that IAV of seasonal and pandemic potential may induce different isoforms of NOX enzymes in the respiratory tract, and that attenuation of virus strain-specific NOX enzymes can be exploited to prevent and/or treat severity of disease. Using three respiratory tract-relevant cell lines (epithelial/A549, endothelial/HULEC, and monoctytic/THP1) and three strains of IAV (H1N1/PR8, H3N2/X31, H1N1/WSN), we found significant upregulation of NOX1 in all three cell lines (e.g.-A549: PR8/55 fold; X31/35 fold; WSN/12,250 fold). Furthermore, in contrast to the epithelial cell line showing NOX1 expression by 4h with peak levels at 16h, the monocytic cell line showed delayed (8h) and sustained (48h) levels of NOX1. Interestingly, inhibition of NOX-isoforms in IAV-infected epithelial cells by diphenyleneiodonium (DPI), at a concentration (25μM), which did not impact cell death, showed significant decrease (75%) in virus triggered NOX1 levels. In addition, NOX-inhibition led to significant decrease in virus-induced chemokines (MCP1, MIP3, MIP1β, RANTES, and IP10) and proinflammatory cytokines (IL1α, IL6, IL8, and TNFα). Furthermore, decline in NOX1 correlated with a modest increase in viral NS1. Taken together, in addition to showing definitive evidence for upregulation of NOX1 in response to subtypes of IAV, our results strongly support a role for NOX1 in IAV-driven inflammation.
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Karpenko, Inna L., Vladimir T. Valuev-Elliston, Olga N. Ivanova, Olga A. Smirnova, and Alexander V. Ivanov. "Peroxiredoxins—The Underrated Actors during Virus-Induced Oxidative Stress." Antioxidants 10, no. 6 (June 18, 2021): 977. http://dx.doi.org/10.3390/antiox10060977.
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Enhanced production of reactive oxygen species (ROS) triggered by various stimuli, including viral infections, has attributed much attention in the past years. It has been shown that different viruses that cause acute or chronic diseases induce oxidative stress in infected cells and dysregulate antioxidant its antioxidant capacity. However, most studies focused on catalase and superoxide dismutases, whereas a family of peroxiredoxins (Prdx), the most effective peroxide scavengers, were given little or no attention. In the current review, we demonstrate that peroxiredoxins scavenge hydrogen and organic peroxides at their physiological concentrations at various cell compartments, unlike many other antioxidant enzymes, and discuss their recycling. We also provide data on the regulation of their expression by various transcription factors, as they can be compared with the imprint of viruses on transcriptional machinery. Next, we discuss the involvement of peroxiredoxins in transferring signals from ROS on specific proteins by promoting the oxidation of target cysteine groups, as well as briefly demonstrate evidence of nonenzymatic, chaperone, functions of Prdx. Finally, we give an account of the current state of research of peroxiredoxins for various viruses. These data clearly show that Prdx have not been given proper attention despite all the achievements in general redox biology.
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Li, Jinlin, Noemi Nagy, Jiangnan Liu, Soham Gupta, Teresa Frisan, Thomas Hennig, Donald P. Cameron, Laura Baranello, and Maria G. Masucci. "The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection." PLOS Pathogens 17, no. 9 (September 20, 2021): e1009954. http://dx.doi.org/10.1371/journal.ppat.1009954.
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Topoisomerases are essential for the replication of herpesviruses but the mechanisms by which the viruses hijack the cellular enzymes are largely unknown. We found that topoisomerase-II (TOP2) is a substrate of the Epstein-Barr virus (EBV) ubiquitin deconjugase BPLF1. BPLF1 co-immunoprecipitated and deubiquitinated TOP2, and stabilized SUMOylated TOP2 trapped in cleavage complexes (TOP2cc), which halted the DNA damage response to TOP2-induced double strand DNA breaks and promoted cell survival. Induction of the productive virus cycle in epithelial and lymphoid cell line carrying recombinant EBV encoding the active enzyme was accompanied by TOP2 deubiquitination, accumulation of TOP2ccs and resistance to Etoposide toxicity. The protective effect of BPLF1 was dependent on the expression of tyrosyl-DNA phosphodiesterase 2 (TDP2) that releases DNA-trapped TOP2 and promotes error-free DNA repair. These findings highlight a previously unrecognized function of BPLF1 in supporting a non-proteolytic pathway for TOP2cc debulking that favors cell survival and virus production.
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HULTBERG, BJÖRN, and FELIX MITELMAN. "Lysosomal enzymes in rat sarcomas induced by 7,12-dimethylbenz(α)anthracene and Rous sarcoma virus." Hereditas 86, no. 1 (February 12, 2009): 103–6. http://dx.doi.org/10.1111/j.1601-5223.1977.tb01216.x.
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Rayavara, Kempaiah, Alexander Kurosky, and Yashoda M. Hosakote. "Respiratory syncytial virus infection induces the release of transglutaminase 2 from human airway epithelial cells." American Journal of Physiology-Lung Cellular and Molecular Physiology 322, no. 1 (January 1, 2022): L1—L12. http://dx.doi.org/10.1152/ajplung.00013.2021.
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Respiratory syncytial virus (RSV) is an important human pathogen that causes severe lower respiratory tract infections in young children, the elderly, and the immunocompromised, yet no effective treatments or vaccines are available. The precise mechanism underlying RSV-induced acute airway disease and associated sequelae are not fully understood; however, early lung inflammatory and immune events are thought to play a major role in the outcome of the disease. Moreover, oxidative stress responses in the airways play a key role in the pathogenesis of RSV. Oxidative stress has been shown to elevate cytosolic calcium (Ca2+) levels, which in turn activate Ca2+-dependent enzymes, including transglutaminase 2 (TG2). Transglutaminase 2 is a multifunctional cross-linking enzyme implicated in various physiological and pathological conditions; however, its involvement in respiratory virus-induced airway inflammation is largely unknown. In this study, we demonstrated that RSV-induced oxidative stress promotes enhanced activation and release of TG2 from human lung epithelial cells as a result of its translocation from the cytoplasm and subsequent release into the extracellular space, which was mediated by Toll-like receptor (TLR)-4 and NF-κB pathways. Antioxidant treatment significantly inhibited RSV-induced TG2 extracellular release and activation via blocking viral replication. Also, treatment of RSV-infected lung epithelial cells with TG2 inhibitor significantly reduced RSV-induced matrix metalloprotease activities. These results suggested that RSV-induced oxidative stress activates innate immune receptors in the airways, such as TLRs, that can activate TG2 via the NF-κB pathway to promote cross-linking of extracellular matrix proteins, resulting in enhanced inflammation.
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Bougie, Isabelle, and Martin Bisaillon. "Inhibition of a metal-dependent viral RNA triphosphatase by decavanadate." Biochemical Journal 398, no. 3 (August 29, 2006): 557–67. http://dx.doi.org/10.1042/bj20060198.
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Paramecium bursaria chlorella virus, a large DNA virus that replicates in unicellular Chlorella-like algae, encodes an RNA triphosphatase which is involved in the synthesis of the RNA cap structure found at the 5′ end of the viral mRNAs. The Chlorella virus RNA triphosphatase is the smallest member of the metal-dependent RNA triphosphatases that include enzymes from fungi, DNA viruses, protozoans and microsporidian parasites. In the present study, we investigated the ability of various vanadate oxoanions to inhibit the phosphohydrolase activity of the enzyme. Fluorescence spectroscopy and CD studies were used to directly monitor the binding of decavanadate to the enzyme. Moreover, competition assays show that decavanadate is a potent non-competitive inhibitor of the phosphohydrolase activity, and mutagenesis studies indicate that the binding of decavanadate does not involve amino acids located in the active site of the enzyme. In order to provide additional insight into the relationship between the enzyme structure and decavanadate binding, we correlated the effect of decavanadate binding on protein structure using both CD and guanidinium chloride-induced denaturation as structural indicators. Our data indicated that no significant modification of the overall protein architecture was occurring upon decavanadate binding. However, both fluorescence spectroscopy and CD experiments clearly revealed that the binding of decavanadate to the enzyme significantly decreased the structural stability of the enzyme. Taken together, these studies provide crucial insights into the inhibition of metal-dependent RNA triphosphatases by decavanadate.
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Turelli, Priscilla, Alexandra Liagre-Quazzola, Bastien Mangeat, Sonia Verp, Stephanie Jost, and Didier Trono. "APOBEC3-Independent Interferon-Induced Viral Clearance in Hepatitis B Virus Transgenic Mice." Journal of Virology 82, no. 13 (April 23, 2008): 6585–90. http://dx.doi.org/10.1128/jvi.00216-08.
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ABSTRACT Interferon (IFN) has been part of the standard treatment of chronic hepatitis B infection for more than 2 decades, yet the mechanism of action of this antiviral remains poorly understood. It was recently observed that members of the human APOBEC family of cytidine deaminases endowed with anti-hepatitis B virus (HBV) activity are upregulated by type I and II IFNs. However, we demonstrated that, in tissue culture, these cellular enzymes are not essential effectors of the anti-HBV action of these cytokines. Here, we show that murine APOBEC3 (muA3) can also block HBV replication. While expressed at low levels in the mouse liver at baseline, muA3 is upregulated upon IFN induction. However, in HBV-transgenic muA3 knockout mice, IFN induction blocked HBV DNA production as efficiently as in control HBV-transgenic muA3-competent animals. We conclude that APOBEC3 is not an essential mediator of the IFN-mediated inhibition of HBV in vivo.
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Louboutin, J. P., L. Agrawal, B. A. S. Reyes, E. J. van Bockstaele, and D. S. Strayer. "Gene delivery of antioxidant enzymes inhibits human immunodeficiency virus type 1 gp120-induced expression of caspases." Neuroscience 214 (July 2012): 68–77. http://dx.doi.org/10.1016/j.neuroscience.2012.03.061.
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Cui, Zhen-Hua, Wen-Lu Bi, Xin-Yi Hao, Peng-Min Li, Ying Duan, M. Andrew Walker, Yan Xu, and Qiao-Chun Wang. "Drought Stress Enhances Up-Regulation of Anthocyanin Biosynthesis in Grapevine leafroll-associated virus 3-Infected in vitro Grapevine (Vitis vinifera) Leaves." Plant Disease 101, no. 9 (September 2017): 1606–15. http://dx.doi.org/10.1094/pdis-01-17-0104-re.
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Reddish-purple coloration on the leaf blades and downward rolling of leaf margins are typical symptoms of grapevine leafroll disease (GLD) in red-fruited grapevine cultivars. These typical symptoms are attributed to the expression of genes encoding enzymes for anthocyanins synthesis, and the accumulation of flavonoids in diseased leaves. Drought has been proven to accelerate development of GLD symptoms in virus-infected leaves of grapevine. However, it is not known how drought affects GLD expression nor how anthocyanin biosynthesis in virus-infected leaves is altered. The present study used HPLC to determine the types and levels of anthocyanins, and applied reverse transcription quantitative polymerase chain reaction (RT-qPCR) to analyze the expression of genes encoding enzymes for anthocyanin synthesis. Plantlets of Grapevine leafroll-associated virus 3 (GLRaV-3)-infected Vitis vinifera ‘Cabernet Sauvignon’ were grown in vitro under PEG-induced drought stress. HPLC found no anthocyanin-related peaks in the healthy plantlets with or without PEG-induced stress, while 11 peaks were detected in the infected plantlets with or without PEG-induced drought stress, but the peaks were significantly higher in infected drought-stressed plantlets. Increased accumulation of total anthocyanin compounds was related to the development of GLD symptoms in the infected plantlets under PEG stress. The highest level of up-regulated gene expression was found in GLRaV-3-infected leaves with PEG-induced drought stress. Analyses of variance and correlation of anthocyanin accumulation with related gene expression levels found that GLRaV-3-infection was the key factor in increased anthocyanin accumulation. This accumulation involved the up-regulation of two key genes, MYBA1 and UFGT, and their expression levels were further enhanced by drought stress.
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Zhou, Guoying, and Bernard Roizman. "Cation-Independent Mannose 6-Phosphate Receptor Blocks Apoptosis Induced by Herpes Simplex Virus 1 Mutants Lacking Glycoprotein D and Is Likely the Target of Antiapoptotic Activity of the Glycoprotein." Journal of Virology 76, no. 12 (June 15, 2002): 6197–204. http://dx.doi.org/10.1128/jvi.76.12.6197-6204.2002.
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ABSTRACT Herpes simplex virus 1 mutants lacking the gene encoding glycoprotein D (gD) and the gD normally present in the envelope of the virus (gD−/− stocks) or mutants lacking the gD gene but containing trans-induced gD in their envelopes (gD−/+) cause apoptosis in human SK-N-SH cells. The gD−/− virions are taken up by endocytosis and are degraded, whereas gD−/+ viruses replicate but produce gD−/− virus. Apoptosis is blocked by delivery of the gD gene in trans. Studies designed to test several hypotheses concerning the role of gD in apoptosis revealed the following. (i) gD−/− and gD−/+ stocks induce fragmentation of cellular DNA in SK-N-SH, HEp-2, HeLa, and Vero cell lines. (ii) Chloroquine blocks apoptosis induced by gD−/− stocks but not by gD−/+ stocks. The drug also rescues gD−/− from degradation. (iii) Cells transduced with cation-independent mannose 6-phosphate receptor (CI-MPR) block apoptosis induced by either gD−/− or gD−/+ virus. (iv) Expression of sequences antisense to the cloned CI-MPR gene induced apoptosis by themselves. Wild-type virus but not gD−/− or gD−/+ stocks of mutant virus blocked apoptosis induced by the expression of CI-MPR antisense sequences. These results exclude the possibility that to block apoptosis, gD must interact with its HveA receptor, a member of the tumor necrosis factor alpha receptor family. Instead, the data suggest that gD blocks the influx of lysosomal enzymes into the endosomal compartment by binding to CI-MPR. This conclusion is consistent with published reports that phosphorylated gD interacts with CI-MPR.
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Karam Anandan, Suresh, Lavanya Rayapu, Subramanyam Darasi, Rani Prameela Devalam, Naga Raju Chamarti, Thirunavukkarasu Chinnasamy, and Lokanatha Valluru. "The investigation of the efficacy of the prodrug DDI-10 against Newcastle disease virus infection in young chicken." Microbes, Infection and Chemotherapy 2 (April 4, 2022): e1333. http://dx.doi.org/10.54034/mic.e1333.
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Introduction. Newcastle disease virus (NDV) is the deadliest virus in the poultry industry. Many RNA viruses induce oxidative stress on the host during its pathogenesis, NDV being one among them. The present study aims to evaluate the protective property of novel phosphorylated DDI-10 in vivo in experimentally infected chicken. Material and methods. NDV induced oxidative damage in the liver and lung were measured by determining antioxidant enzyme levels, protein oxidation and nitration using ELISA, Western blot and immuno co-localization assay. Results. Glutathione dependent enzymes GPx, GST, and GR were significantly decreased in the NDV infected group due to pathogenesis; DDI-10 treatment was shown to significantly increase this reduced enzyme activity. In comparison to the healthy control group, protein oxidation and nitration levels were significantly increased in the NDV infected group. In the DDI-10 treated group, the oxidation and nitration levels were decreased compared to the NDV infected group. Further estimation of protein nitration and oxidation in western blot and immune co-localization assays correlated with the ELISA results; an intensified band was demonstrated in the NDV infected tissue group, in addition to a high number of co-localized cells being present in immunofluorescence-stained sections compared to control chicken tissues. These alterations were noticeably reduced in novel phosphorylated DDI-10 treatment group. Conclusions. These results suggest that DDI-10 mitigates NDV induced oxidative stress, subsequently exerting an ameliorative effect against NDV pathogenesis.
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Gui, Yue-Jing, Wen-Qi Zhang, Dan-Dan Zhang, Lei Zhou, Dylan P. G. Short, Jie Wang, Xue-Feng Ma, et al. "A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses." Molecular Plant-Microbe Interactions® 31, no. 2 (February 2018): 260–73. http://dx.doi.org/10.1094/mpmi-06-17-0136-r.
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Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain–containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V. dahliae Vd991. Functional analyses demonstrated that only VdCUT11, as purified protein, induced cell death and triggered defense responses in Nicotiana benthamiana, cotton, and tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner. Furthermore, coinfiltration assays revealed that the carbohydrate-binding module family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an important secreted enzyme and virulence factor that elicits plant defense responses in the absence of VdCBM1.
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Li, Zhe-Xin, Min Chen, Yu-Xiang Miao, Qiang Li, Yun Ren, Wen-Lin Zhang, Jian-Bin Lan, and Yi-Qing Liu. "The role of AcPGIP in the kiwifruit (Actinidia chinensis) response to Botrytis cinerea." Functional Plant Biology 48, no. 12 (2021): 1254. http://dx.doi.org/10.1071/fp21054.
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Kiwifruit (Actinidia chinensis) is rich in nutritional and medicinal value. However, the organism responsible for grey mould, Botrytis cinerea, causes great economic losses and food safety problems to the kiwifruit industry. Understanding the molecular mechanism underlying postharvest kiwifruit responses to B. cinerea is important for preventing grey mould decay and enhancing resistance breeding. Kiwifruit cv. ‘Hongyang’ was used as experimental material. The AcPGIP gene was cloned and virus-induced gene silencing (VIGS) was used to explore the function of the polygalacturonase inhibiting protein (PGIP) gene in kiwifruit resistance to B. cinerea. Virus-induced silencing of AcPGIP resulted in enhanced susceptibility of kiwifruit to B. cinerea. Antioxidant enzymes, secondary metabolites and endogenous hormones were analysed to investigate kiwifruit responses to B. cinerea infection. Kiwifruit effectively activated antioxidant enzymes and secondary metabolite production in response to B. cinerea, which significantly increased Indole-3-acetic acid (IAA), gibberellin 3 (GA3) and abscisic acid (ABA) content relative to those in uninfected fruit. Silencing of AcPGIP enabled kiwifruit to quickly activate hormone-signaling pathways through an alternative mechanism to trigger defence responses against B. cinerea infection. These results expand our understanding of the regulatory mechanism for disease resistance in kiwifruit; further, they provide gene-resource reserves for molecular breeding of kiwifruit for disease resistance.
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Golem, Sheetal, and James N. Culver. "Tobacco mosaic virus Induced Alterations in the Gene Expression Profile of Arabidopsis thaliana." Molecular Plant-Microbe Interactions® 16, no. 8 (August 2003): 681–88. http://dx.doi.org/10.1094/mpmi.2003.16.8.681.
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In this study, mRNA profiles generated from cDNA microarrays were used to identify gene expression changes in Arabidopsis thaliana ecotype Shahdara infected with Tobacco mosaic virus (TMV). Shahdara is a susceptible TMV host, permitting rapid accumulations of virus in both inoculated and systemic tissues, accompanied by defined disease symptoms that include stunting, necrosis, and leaf curling. Gene expression profiles were monitored in whole tissues of inoculated leaves at four days postinoculation (dpi) and in systemically infected leaves at 14 dpi. Microarrays contained cDNAs representing between 8,000 and 10,000 Arabidopsis genes. Expression analysis identified 68 genes that displayed significant and consistent changes in expression levels, either up or down, in either TMV inoculated or systemically infected tissues, or both. Identified TMV-responsive genes encode a diverse array of functional proteins that include transcription factors, antioxidants, metabolic enzymes, and transporters. Thus, the TMV infection process has a significant impact on a wide array of cellular processes that likely reflect the biochemical and physiological changes involved in the development of this disease syndrome.
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Mishra, Suresh, Geetika Bassi, and BL Grégoire Nyomba. "Inter-proteomic posttranslational modifications of the SARS-CoV-2 and the host proteins ‒ A new frontier." Experimental Biology and Medicine 246, no. 7 (January 19, 2021): 749–57. http://dx.doi.org/10.1177/1535370220986785.
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Posttranslational modification of proteins, which include both the enzymatic alterations of protein side chains and main-chain peptide bond connectivity, is a fundamental regulatory process that is crucial for almost every aspects of cell biology, including the virus-host cell interaction and the SARS-CoV-2 infection. The posttranslational modification of proteins has primarily been studied in cells and tissues in an intra-proteomic context (where both substrates and enzymes are part of the same species). However, the inter-proteomic posttranslational modifications of most of the SARS-CoV-2 proteins by the host enzymes and vice versa are largely unexplored in virus pathogenesis and in the host immune response. It is now known that the structural spike (S) protein of the SARS-CoV-2 undergoes proteolytic priming by the host serine proteases for entry into the host cells, and N- and O-glycosylation by the host cell enzymes during virion packaging, which enable the virus to spread. New evidence suggests that both SARS-CoV-2 and the host proteins undergo inter-proteomic posttranslational modifications, which play roles in virus pathogenesis and infection-induced immune response by hijacking the host cell signaling. The purpose of this minireview is to bring attention of the scientific community to recent cutting-edge discoveries in this understudied area. It is likely that a better insight into the molecular mechanisms involved may open new research directions, and thereby contribute to novel therapeutic modality development against the SARS-CoV-2. Here we briefly discuss the rationale and touch upon some unanswered questions in this context, especially those that require attention from the scientific community.
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Pappi, Polyxeni, Nikolaos Nikoloudakis, Dimitrios Fanourakis, Antonios Zambounis, Costas Delis, and Georgios Tsaniklidis. "Differential Triggering of the Phenylpropanoid Biosynthetic Pathway Key Genes Transcription upon Cold Stress and Viral Infection in Tomato Leaves." Horticulturae 7, no. 11 (November 2, 2021): 448. http://dx.doi.org/10.3390/horticulturae7110448.
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Plants develop a plethora of defense strategies during their acclimation and interactions with various environmental stresses. Secondary metabolites play a pivotal role in the processes during stress acclimation, therefore deciphering their relevant responses exchange the interpretation of the underlying molecular mechanisms that may contribute to improved adaptability and efficacy. In the current study, tomato plants were exposed to short-term cold stress (5 °C for 16 h) or inoculated (20 d) with either Cucumber Mosaic Virus (CMV) or Potato Virus Y (PVY). Responses were recorded via the assessments of leaf total phenolic (TP) content, total flavonoid (TF) levels, and phenylalanine ammonia-lyase (PAL) enzyme activity. The transcription of the gene families regulating the core phenylpropanoid biosynthetic pathway (PBP) at an early (PAL, cinnamic acid 4-hydroxylase, 4-coumarate-CoA ligase) or late (chalcone synthase and flavonol synthase) stage was also evaluated. The results showed that cold stress stimulated an increase in TP and TF contents, while PAL enzyme activity was also elevated compared to viral infection. Besides genes transcription of the enzymes involved in the core PBP was mostly induced by cold stress, whereas transcription of the genes regulating flavonoid biosynthesis was mainly triggered by viral infection. In conclusion, abiotic and biotic stressors induced differential regulation of the core PBP and flavonoid biosynthetic metabolism. Taking the above into consideration, our results highlight the complexity of tomato responses to diverse stimuli allowing for better elucidation of stress tolerance mechanisms at this crop.
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Alvarado-Facundo, Esmeralda, Yamei Gao, Rosa María Ribas-Aparicio, Alicia Jiménez-Alberto, Carol D. Weiss, and Wei Wang. "Influenza Virus M2 Protein Ion Channel Activity Helps To Maintain Pandemic 2009 H1N1 Virus Hemagglutinin Fusion Competence during Transport to the Cell Surface." Journal of Virology 89, no. 4 (December 3, 2014): 1975–85. http://dx.doi.org/10.1128/jvi.03253-14.
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ABSTRACTThe influenza virus hemagglutinin (HA) envelope protein mediates virus entry by first binding to cell surface receptors and then fusing viral and endosomal membranes during endocytosis. Cleavage of the HA precursor (HA0) into a surface receptor-binding subunit (HA1) and a fusion-inducing transmembrane subunit (HA2) by host cell enzymes primes HA for fusion competence by repositioning the fusion peptide to the newly created N terminus of HA2. We previously reported that the influenza virus M2 protein enhances pandemic 2009 influenza A virus [(H1N1)pdm09] HA-pseudovirus infectivity, but the mechanism was unclear. In this study, using cell-cell fusion and HA-pseudovirus infectivity assays, we found that the ion channel function of M2 was required for enhancement of HA fusion and HA-pseudovirus infectivity. The M2 activity was needed only during HA biosynthesis, and proteolysis experiments indicated that M2 proton channel activity helped to protect (H1N1)pdm09 HA from premature conformational changes as it traversed low-pH compartments during transport to the cell surface. While M2 has previously been shown to protect avian influenza virus HA proteins of the H5 and H7 subtypes that have polybasic cleavage motifs, this study demonstrates that M2 can protect HA proteins from human H1N1 strains that lack a polybasic cleavage motif. This finding suggests that M2 proton channel activity may play a wider role in preserving HA fusion competence among a variety of HA subtypes, including HA proteins from emerging strains that may have reduced HA stability.IMPORTANCEInfluenza virus infects cells when the hemagglutinin (HA) surface protein undergoes irreversible pH-induced conformational changes after the virus is taken into the cell by endocytosis. HA fusion competence is primed when host cell enzymes cleave the HA precursor. The proton channel function of influenza virus M2 protein has previously been shown to protect avian influenza virus HA proteins that contain a polybasic cleavage site from pH-induced conformational changes during biosynthesis, but this effect is less well understood for human influenza virus HA proteins that lack polybasic cleavage sites. Using assays that focus on HA entry and fusion, we found that the M2 protein also protects (H1N1)pdm09 influenza A virus HA from premature conformational changes as it transits low-pH compartments during biosynthesis. This work suggests that M2 may play a wider role in preserving HA function in a variety of influenza virus subtypes that infect humans and may be especially important for HA proteins that are less stable.
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Yin, Limin, Xiuhai Gan, Jing Shi, Ningning Zan, Awei Zhang, Xiaoli Ren, Miao Li, Dandan Xie, Deyu Hu, and Baoan Song. "Induced Resistance Mechanism of Novel Curcumin Analogs Bearing a Quinazoline Moiety to Plant Virus." International Journal of Molecular Sciences 19, no. 12 (December 15, 2018): 4065. http://dx.doi.org/10.3390/ijms19124065.
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Plant immune activators can protect crops from plant virus pathogens by activating intrinsic immune mechanisms in plants and are widely used in agricultural production. In our previous work, we found that curcumin analogs exhibit excellent biological activity against plant viruses, especially protective activity. Inspired by these results, the active substructure of pentadienone and quinazoline were spliced to obtain curcumin analogs as potential exogenously induced resistant molecule. Bioassay results showed that compound A13 exhibited excellent protective activity for tobacco to against Tobacco mosaic virus (TMV) at 500 μg/mL, with a value of 70.4 ± 2.6% compared with control treatments, which was better than that of the plant immune activator chitosan oligosaccharide (49.0 ± 5.9%). The protective activity is due to compound A13 inducing tobacco resistance to TMV, which was related to defense-related enzymes, defense-related genes, and photosynthesis. This was confirmed by the up-regulated expression of proteins that mediate stress responses and oxidative phosphorylation.
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Fu, Xiaotian, Xinyi Jiang, Xinye Chen, Liqian Zhu, and Gaiping Zhang. "The Differential Expression of Mitochondrial Function-Associated Proteins and Antioxidant Enzymes during Bovine Herpesvirus 1 Infection: A Potential Mechanism for Virus Infection-Induced Oxidative Mitochondrial Dysfunction." Mediators of Inflammation 2019 (March 18, 2019): 1–10. http://dx.doi.org/10.1155/2019/7072917.
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Reactive oxidative species (ROS) are important inflammatory mediators. Electrons escaping from the mitochondrial electron transport chain (ETC) during oxidative phosphorylation (OXPHOS) in the mitochondrial respiratory chain (RC) complexes contribute to ROS production. The cellular antioxidant enzymes are important for maintaining ROS release at the physiological levels. It has been reported that BoHV-1 infection induces overproduction of ROS and oxidative mitochondrial dysfunction in cell cultures. In this study, we found that chemical interruption of RC complexes by TTFA (an inhibitor of RC complex II), NaN3 (an inhibitor of RC complex IV), and oligomycin A (an inhibitor of ATP synthase) consistently decreased virus productive infection, suggesting that the integral processes of RC complexes are important for the virus replication. The virus infection significantly increased the expression of subunit SDHB (succinate dehydrogenase) and MTCO1 (cytochrome c oxidase subunit I), critical components of RC complexes II and IV, respectively. The expression of antioxidant enzymes including superoxide dismutase 1 (SOD1), SOD2, catalase (CAT), and glutathione peroxidase 4 (GPX4) was differentially affected following the virus infection. The protein TFAM (transcription factor A, mitochondrial) stimulated by either nuclear respiratory factor 1 (NRF1) or NRF2 is a key regulator of mitochondrial biogenesis. Interestingly, the virus infection at the late stage (at 16 h after infection) stimulated TFAM expression but decreased the levels of both NRF1 and NRF2, indicating that virus infection activated TFAM signaling independent of either NRF1 or NRF2. Overall, this study provided evidence that BoHV-1 infection altered the expression of molecules associated with RC complexes, antioxidant enzymes, and mitochondrial biogenesis-related signaling NRF1/NRF2/TFAM, which correlated with the previous report that virus infection induces ROS overproduction and mitochondrial dysfunction.
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Bajrovic, Irnela, Stephen C. Schafer, Dwight K. Romanovicz, and Maria A. Croyle. "Novel technology for storage and distribution of live vaccines and other biological medicines at ambient temperature." Science Advances 6, no. 10 (March 2020): eaau4819. http://dx.doi.org/10.1126/sciadv.aau4819.
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A novel, thin-film platform that preserves live viruses, bacteria, antibodies, and enzymes without refrigeration for extended periods of time is described. Studies with recombinant adenovirus in an optimized formulation that supports recovery of live virus through 16 freeze-thaw cycles revealed that production of an amorphous solid with a glass transition above room temperature and nitrogen-hydrogen bonding between virus and film components are critical determinants of stability. Administration of live influenza virus in the optimized film by the sublingual and buccal routes induced antibody-mediated immune responses as good as or better than those achieved by intramuscular injection. This work introduces the possibility of improving global access to a variety of medicines by offering a technology capable of reducing costs of production, distribution, and supply chain maintenance.
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García-Marcos, Alberto, Remedios Pacheco, Justo Martiáñez, Pablo González-Jara, José Ramón Díaz-Ruíz, and Francisco Tenllado. "Transcriptional Changes and Oxidative Stress Associated with the Synergistic Interaction Between Potato virus X and Potato virus Y and Their Relationship with Symptom Expression." Molecular Plant-Microbe Interactions® 22, no. 11 (November 2009): 1431–44. http://dx.doi.org/10.1094/mpmi-22-11-1431.
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Many virus diseases of economic importance to agriculture result from mixtures of different pathogens invading the host at a given time. This contrasts with the relatively scarce studies available on the molecular events associated with virus–host interactions in mixed infections. Compared with single infections, co-infection of Nicotiana benthamiana with Potato virus X (PVX) and Potato virus Y (PVY) resulted in increased systemic symptoms (synergism) that led to necrosis of the newly emerging leaves and death of the plant. A comparative transcriptional analysis was undertaken to identify quantitative and qualitative differences in gene expression during this synergistic infection and correlate these changes with the severe symptoms it caused. Global transcription profiles of doubly infected leaves were compared with those from singly infected leaves using gene ontology enrichment analysis and metabolic pathway annotator software. Functional gene categories altered by the double infection comprise suites of genes regulated coordinately, which are associated with chloroplast functions (downregulated), protein synthesis and degradation (upregulated), carbohydrate metabolism (upregulated), and response to biotic stimulus and stress (upregulated). The expressions of reactive oxygen species–generating enzymes as well as several mitogen-activated protein kinases were also significantly induced. Accordingly, synergistic infection induced a severe oxidative stress in N. benthamiana leaves, as judged by increases in lipid peroxidation and by the generation of superoxide radicals in chloroplasts, which correlated with the misregulation of antioxidative genes in microarray data. Interestingly, expression of genes encoding oxylipin biosynthesis was uniquely upregulated by the synergistic infection. Virus-induced gene silencing of α-dioxygenase1 delayed cell death during PVX–PVY infection.
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Ansar, Maria, Yue Qu, Teodora Ivanciuc, Roberto P. Garofalo, and Antonella Casola. "Lack of Type I Interferon Signaling Ameliorates Respiratory Syncytial Virus-Induced Lung Inflammation and Restores Antioxidant Defenses." Antioxidants 11, no. 1 (December 28, 2021): 67. http://dx.doi.org/10.3390/antiox11010067.
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Respiratory syncytial virus (RSV) infection in mouse and human lung is associated with pathogenic inflammation and oxidative injury. RSV impairs antioxidant responses by increasing the degradation of transcription factor NF-E2-related factor 2 (NRF2), which controls the expression of several antioxidant enzymes (AOEs). In addition to its protective effects, type I IFNs have been increasingly recognized as important mediators of host pathogenic responses during acute respiratory viral infections. We used a mouse model of RSV infection to investigate the effect of lack of type I interferon (IFN) receptor on viral-mediated clinical disease, airway inflammation, NRF2 expression, and antioxidant defenses. In the absence of type I IFN signaling, RSV-infected mice showed significantly less body weight loss and airway obstruction, as well as a significant reduction in cytokine and chemokine secretion and airway inflammation. Lack of type I IFN receptor was associated with greatly reduced virus-induced promyelocytic leukemia lung protein expression, which we showed to be necessary for virus-induced NRF2 degradation in a cell model of infection, resulting in restoration of NRF2 levels, AOE expression, and airway antioxidant capacity. Our data support the concept that modulation of type I IFN production and/or signaling could represent an important therapeutic strategy to ameliorate severity of RSV-induced lung disease.
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Cai, Ying, Yi-Fang Li, Lu-Ping Tang, Bun Tsoi, Min Chen, Huan Chen, Xiao-Mei Chen, Rui-Rong Tan, Hiroshi Kurihara, and Rong-Rong He. "A New Mechanism of Vitamin C Effects on A/FM/1/47(H1N1) Virus-Induced Pneumonia in Restraint-Stressed Mice." BioMed Research International 2015 (2015): 1–12. http://dx.doi.org/10.1155/2015/675149.
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It is well known that vitamin C could protect against influenza infection, but little is known about the mechanisms. This study aimed to investigate the influence and possible mechanisms of vitamin C on pneumonia induced by influenza virus in stressed mice. Results showed that restraint stress significantly increased the mortality and the severity of pneumonia in mice caused by A/FM/1/47(H1N1) virus infection, which was attenuated by oral administration of vitamin C (125 and 250 mg/kg). Moreover, vitamin C administration significantly decreased expression of susceptibility genes, including mitochondrial antiviral signaling (MAVS) and interferon regulatory factor 3 (IRF3), and increased expression of NF-κB. These work in conjunction to induce type I interferons (IFNs) and elicit innate antiviral response as key factors in RIG-I-mediated signal transduction pathway. The above effects of vitamin C were further found to relate with inhibition of excess CORT synthesis by regulating steroid hydroxylating enzymes in adrenal gland. In conclusion, the protective effects of vitamin C on influenza virus-caused pneumonia might be related to its inhibition of CORT synthesis, which reduces the susceptibility to influenza viral infection in restraint-stressed mice. These findings provide a new mechanism for the effects of vitamin C on influenza virus-induced pneumonia in restraint-stressed mice.
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Nicolas, Armel, Nathalie Alazard-Dany, Coline Biollay, Loredana Arata, Nelly Jolinon, Lauriane Kuhn, Myriam Ferro, et al. "Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments." Journal of Virology 84, no. 17 (June 23, 2010): 8871–87. http://dx.doi.org/10.1128/jvi.00725-10.
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ABSTRACT Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase δ was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.
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Sánchez, Glòria, Lluís Aragonès, M. Isabel Costafreda, Enric Ribes, Albert Bosch, and Rosa M. Pintó. "Capsid Region Involved in Hepatitis A Virus Binding to Glycophorin A of the Erythrocyte Membrane." Journal of Virology 78, no. 18 (September 15, 2004): 9807–13. http://dx.doi.org/10.1128/jvi.78.18.9807-9813.2004.
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ABSTRACT Hepatitis A virus (HAV) has previously been reported to agglutinate human red blood cells at acidic pHs. Treatment of erythrocytes with different enzymes and chemical reagents indicated that HAV attachment is mediated through an interaction with sialylglycoproteins. HAV hemagglutination could be blocked by incubating the virus with glycophorin A, indicating that this sialylglycoprotein is the erythrocyte receptor. The number of receptors used was estimated to be around 500 per cell. At the same time, HAV-induced hemagglutination could also be blocked by either monoclonal antibody H7C27 or an anti-VP3(102-121) ascitic fluid, indicating that lysine 221 of VP1 and the surrounding VP3 residues lining the capsid pit are involved in HAV binding to erythrocytes.
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Komissarov, Alexey A., Maria A. Karaseva, Marina P. Roschina, Andrey V. Shubin, Nataliya A. Lunina, Sergey V. Kostrov, and Ilya V. Demidyuk. "Individual Expression of Hepatitis A Virus 3C Protease Induces Ferroptosis in Human Cells In Vitro." International Journal of Molecular Sciences 22, no. 15 (July 23, 2021): 7906. http://dx.doi.org/10.3390/ijms22157906.
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Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD, including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. Here, we expressed 3Cpro in HEK293, HeLa, and A549 human cell lines to characterize 3Cpro-induced cell death morphologically and biochemically using flow cytometry and fluorescence microscopy. We found that dead cells demonstrated necrosis-like morphological changes including permeabilization of the plasma membrane, loss of mitochondrial potential, as well as mitochondria and nuclei swelling. Additionally, we showed that 3Cpro-induced cell death was efficiently blocked by ferroptosis inhibitors and was accompanied by intense lipid peroxidation. Taken together, these results indicate that 3Cpro induces ferroptosis upon its individual expression in human cells. This is the first demonstration that a proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.
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Shpagina, L. A., O. S. Kotova, I. S. Shpagin, D. A. Gerasimenko, G. V. Kuznetsova, S. A. Karmanovskaya, E. M. Loktin, et al. "Clinical and molecular features of virus-induced acute exacerbations of chronic obstructive pulmonary diseas." Meditsinskiy sovet = Medical Council 16, no. 18 (October 14, 2022): 30–39. http://dx.doi.org/10.21518/2079-701x-2022-16-18-30-39.
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Introduction. Inflammation in viral-induced acute exacerbations of chronic obstructive pulmonary disease (COPD) is not studied enough.The aim was to establish molecular pattern of inflammation in viral-induced acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in comparison with bacterial AECOPD and to reveal associations with AECOPD phenotype and subsequent COPD progression.Materials and methods. Subjects hospitalized with acute exacerbations of COPD (AECOPD) of which 60 were viral, 60 were bacterial and 60 were viral-bacterial were recruited to single center prospective (52 weeks) cohort study. Control group – 30 healthy people. COPD were diagnosed previously during stable phase of the disease according to spirographic criteria. Viral AECOPD were confirmed by detection of RNA of influenza A and B, respiratory syncytial virus, rhinovirus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in sputum or bronchoalveolar lavage fluid (BALF) using reverse transcription-polymerase chain reaction (RT-PCR). Bacterial AECOPD were confirmed by sputum/BALF neutrophilia or elevated blood procalcitonin levels or by detecting bacteria by standard culture method. Plasma concentrations of cytokines, fibrotic markers, enzymes were measured by enzyme-linked immunosorbent assay, plasma fibrinogen – by Clauss method. Complex lung function investigation, Dopplerechocardiography, subsequent AECOPD assessment were done. Kruskal-Wallis and chi-square test were used to compare groups, Cox regression and linear regression – to explore relationships.Results. Viral AECOPD were characterized by highest plasma concentrations of Eosinophilic cationic protein (62,3 (52,4; 71,0) ng/ml)), interleukin-5 (IL-5) (11,3 (8,4; 15,9) pg/ml), fibroblast growth factor-2 (FGF-2) (10,4 (6,2; 14,9) pg/ml), transforming growth factor-β1 (TGF-β1) (922,4 (875,7; 953,8) pg/ml), hyaluronic acid (185,4 (172,8; 196,3) ng/ml), amino-terminal propeptide of type III procollagen (PIIINP) (249,2 (225,1; 263,7) ng/ml), matrix metalloproteinase-1 (MMP-1) (235,2 (208,6; 254,9) pg/ml). Levels of IL-5 during AE COPD was the predictor of FEV1, bronchodilation coefficient, subsequent exacerbations at remote period, fibrinogen was associated with FEV1, PIIINP and FGF-2 with DLco, PaO2, mean pulmonary artery pressure (mPAP), exacerbations, MMP-1 – with mPAP.Conclusions. In virus-induced AECOPD inflammation pattern differed from those in bacterial one and associated with AECOPD phenotype and COPD phenotype at the stable phase.
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Gammon, Don B., and David H. Evans. "The 3′-to-5′ Exonuclease Activity of Vaccinia Virus DNA Polymerase Is Essential and Plays a Role in Promoting Virus Genetic Recombination." Journal of Virology 83, no. 9 (February 18, 2009): 4236–50. http://dx.doi.org/10.1128/jvi.02255-08.
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ABSTRACT Poxviruses are subjected to extraordinarily high levels of genetic recombination during infection, although the enzymes catalyzing these reactions have never been identified. However, it is clear that virus-encoded DNA polymerases play some unknown yet critical role in virus recombination. Using a novel, antiviral-drug-based strategy to dissect recombination and replication reactions, we now show that the 3′-to-5′ proofreading exonuclease activity of the viral DNA polymerase plays a key role in promoting recombination reactions. Linear DNA substrates were prepared containing the dCMP analog cidofovir (CDV) incorporated into the 3′ ends of the molecules. The drug blocked the formation of concatemeric recombinant molecules in vitro in a process that was catalyzed by the proofreading activity of vaccinia virus DNA polymerase. Recombinant formation was also blocked when CDV-containing recombination substrates were transfected into cells infected with wild-type vaccinia virus. These inhibitory effects could be overcome if CDV-containing substrates were transfected into cells infected with CDV-resistant (CDVr) viruses, but only when resistance was linked to an A314T substitution mutation mapping within the 3′-to-5′ exonuclease domain of the viral polymerase. Viruses encoding a CDVr mutation in the polymerase domain still exhibited a CDV-induced recombination deficiency. The A314T substitution also enhanced the enzyme's capacity to excise CDV molecules from the 3′ ends of duplex DNA and to recombine these DNAs in vitro, as judged from experiments using purified mutant DNA polymerase. The 3′-to-5′ exonuclease activity appears to be an essential virus function, and our results suggest that this might be because poxviruses use it to promote genetic exchange.
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Glanz, Anna, Sukanya Chakravarty, Merina Varghese, Anita Kottapalli, Shumin Fan, Ritu Chakravarti, and Saurabh Chattopadhyay. "Transcriptional and Non-Transcriptional Activation, Posttranslational Modifications, and Antiviral Functions of Interferon Regulatory Factor 3 and Viral Antagonism by the SARS-Coronavirus." Viruses 13, no. 4 (March 29, 2021): 575. http://dx.doi.org/10.3390/v13040575.
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The immune system defends against invading pathogens through the rapid activation of innate immune signaling pathways. Interferon regulatory factor 3 (IRF3) is a key transcription factor activated in response to virus infection and is largely responsible for establishing an antiviral state in the infected host. Studies in Irf3−/− mice have demonstrated the absence of IRF3 imparts a high degree of susceptibility to a wide range of viral infections. Virus infection causes the activation of IRF3 to transcribe type-I interferon (e.g., IFNβ), which is responsible for inducing the interferon-stimulated genes (ISGs), which act at specific stages to limit virus replication. In addition to its transcriptional function, IRF3 is also activated to trigger apoptosis of virus-infected cells, as a mechanism to restrict virus spread within the host, in a pathway called RIG-I-like receptor-induced IRF3 mediated pathway of apoptosis (RIPA). These dual functions of IRF3 work in concert to mediate protective immunity against virus infection. These two pathways are activated differentially by the posttranslational modifications (PTMs) of IRF3. Moreover, PTMs regulate not only IRF3 activation and function, but also protein stability. Consequently, many viruses utilize viral proteins or hijack cellular enzymes to inhibit IRF3 functions. This review will describe the PTMs that regulate IRF3′s RIPA and transcriptional activities and use coronavirus as a model virus capable of antagonizing IRF3-mediated innate immune responses. A thorough understanding of the cellular control of IRF3 and the mechanisms that viruses use to subvert this system is critical for developing novel therapies for virus-induced pathologies.
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Eisenlohr, L. C., W. Gerhard, and C. J. Hackett. "Acid-induced conformational modification of the hemagglutinin molecule alters interaction of influenza virus with antigen-presenting cells." Journal of Immunology 141, no. 6 (September 15, 1988): 1870–76. http://dx.doi.org/10.4049/jimmunol.141.6.1870.
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Abstract Brief exposure of influenza virus to pH 5 was found to have extensive effects upon presentation of viral Th cell antigenic determinants. This acidity, comparable to that encountered in host cell endosomes, was known to effect conformational changes in the viral hemagglutinin (HA) which alter the molecule's fusion activity, antigenicity, and susceptibility to enzymes. Three major effects of low pH upon presentation of viral T cell determinants were observed: first, acid pretreatment permitted presentation by pre-fixed APC of two of three linear T cell sites of the HA molecule, bypassing the APC activity required to present untreated virus; second, the two determinants presented in this manner disappeared rapidly from APC surfaces; third, acid-pretreated virus was not efficiently utilized by active APC in the normal pathway of viral antigen presentation. These observations suggest that the pH-induced conformational transition of HA may constitute sufficient processing for certain linear determinants of the molecule and additionally influences the processes involved in the general formation and presentation of viral T cell sites.
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Serkedjieva, Julia, Tsvetanka Stefanova, and Ekaterina Krumova. "A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection." Zeitschrift für Naturforschung C 65, no. 5-6 (June 1, 2010): 419–28. http://dx.doi.org/10.1515/znc-2010-5-616.
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The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.
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Zhang, Jisong, Liping Huang, Zhuo Zhang, Zhanhong Zhang, Deyong Zhang, Youjun Zhang, Xiaobin Shi, and Yong Liu. "Tomato Chlorosis Virus (ToCV) Infection Induced the Resistance of Bemisia tabaci to Two Insecticides: Pyrethroids and Flupyradifurone." Horticulturae 9, no. 1 (January 5, 2023): 68. http://dx.doi.org/10.3390/horticulturae9010068.
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Insect vectors and insect-borne plant viruses seriously endanger the safety of agricultural production. An insecticide is one of the main methods to prevent insect-borne virus transmission. However, the curious relationship between the resistance of insect vectors and arboviruses has been less studied. In this study, the effect of Tomato chlorosis virus (ToCV) on the insecticide resistance of Bemisia tabaci MED was studied. It was found that the detoxification cytochrome P450, glutathione S-transferase, and carboxylesterase-related genes in ToCV-infected B. tabaci were upregulated. The activity of the three detoxification enzymes all increased at the same time, after 48 h of virus acquisition, with the activity of carboxylesterase being the most pronounced. It was found that cytochrome P450 and glutathione S-transferase activity was the least. ToCV led to the reduced sensitivity of B. tabaci MED to pyrethroids and flupyradifurone. Therefore, it was proven that the insect-borne plant virus ToCV shows the possibility of enhancing insect-borne insecticide resistance.
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Chu, Ki-Back, Hae-Ahm Lee, Hae-Ji Kang, Eun-Kyung Moon, and Fu-Shi Quan. "Preliminary Trichinella spiralis Infection Ameliorates Subsequent RSV Infection-Induced Inflammatory Response." Cells 9, no. 5 (May 25, 2020): 1314. http://dx.doi.org/10.3390/cells9051314.
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Respiratory syncytial virus (RSV) infection affects the lives of neonates throughout the globe, causing a high rate of mortality upon hospital admission. Yet, therapeutic options to deal with this pulmonary pathogen are currently limited. Helminth therapy has been well received for its immunomodulatory role in hosts, which are crucial for mitigating a multitude of diseases. Therefore, in this study, we used the helminth Trichinella spiralis and assessed its capabilities for modulating RSV infection as well as the inflammatory response induced by it in mice. Our results revealed that RSV-specific antibody responses were enhanced by pre-existing T. spiralis infection, which also limited pulmonary viral replication. Diminished lung inflammation, indicated by reduced pro-inflammatory cytokines and inflammatory cell influx was confirmed, as well as through histopathological assessment. We observed that inflammation-associated nuclear factor kappa-light-chain enhancement of activated B cells (NF-κB) and its phosphorylated forms were down-regulated, whereas antioxidant-associated nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression was upregulated in mice co-infected with T. spiralis and RSV. Upregulated Nrf2 expression contributed to increased antioxidant enzyme expression, particularly NQO1 which relieved the host of oxidative stress-induced pulmonary inflammation caused by RSV infection. These findings indicate that T. spiralis can mitigate RSV-induced inflammation by upregulating the expression of antioxidant enzymes.
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Terekhov, SS, VI Shmygarev, KV Purtov, IV Smirnov, IV Yampolsky, and AS Tsarkova. "Drug design strategies for the treatment of coronavirus infection." Bulletin of Russian State Medical University, no. 2022(6) (December 2022): 89–91. http://dx.doi.org/10.24075/brsmu.2022.067.
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The increasing size and density of the human population is leading to an increasing risk of infectious diseases that threaten to spread yet another pandemics. The widespread use of vaccination has reduced morbidity and mortality associated with viral infections and in some cases eradicated the virus from the population entirely. Regrettably, some virus species retain the ability to mutate rapidly and thus evade the vaccine-induced immune response. New antiviral drugs are therefore needed for the treatment and prevention of viral diseases. Modern research into the structures and properties of viral proteases, which are of key importance in the life cycle of viruses, makes it possible, in our opinion, to turn these enzymes into promising targets for the development of effective viral disease control methods.
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Monne Rodriguez, Josep Maria, Gail Leeming, Kernt Köhler, and Anja Kipar. "Feline Herpesvirus Pneumonia: Investigations Into the Pathogenesis." Veterinary Pathology 54, no. 6 (August 16, 2017): 922–32. http://dx.doi.org/10.1177/0300985817720982.
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Feline herpesvirus type 1 (FeHV-1) is one of the etiological agents of feline respiratory disease. FeHV-1 is an epitheliotropic and cytopathic virus that mainly causes rhinitis and conjunctivitis, although pneumonia is also occasionally seen. In this study, the authors investigated the pathogenesis of FeHV-1-associated pneumonia, comparing natural cases with viral infection of tracheal ring and cell cultures in vitro, using histology, immunohistology, double immunofluorescence, and transmission electron microscopy as investigative tools. The results confirm that FeHV-1 targets both respiratory epithelial cells and pneumocytes and indicate that FeHV-1 pneumonia is the consequence of continuous cell-to-cell viral spread from the upper airways via the trachea into the lungs. They provide strong evidence that FeHV-1–infected cells die primarily via apoptosis, following loss of cell-to-cell contact, rounding, and detachment. However, virus-induced lesions in vivo are dominated by marked neutrophil infiltration and extensive necrosis with less prominent apoptosis; in the airways, the tissue necrosis can extend into the submucosa. The necrosis appears to result from virus-induced neutrophil influx and release of proteolytic enzymes, such as matrix metalloproteinase-9, from the neutrophils.
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Chiang, Cindy, Guanqun Liu, and Michaela U. Gack. "Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation." Viruses 13, no. 2 (January 26, 2021): 182. http://dx.doi.org/10.3390/v13020182.
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Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.
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Wang, Meiling, Shuoxin Zhang, and Fei Ding. "Melatonin Mitigates Chilling-Induced Oxidative Stress and Photosynthesis Inhibition in Tomato Plants." Antioxidants 9, no. 3 (March 6, 2020): 218. http://dx.doi.org/10.3390/antiox9030218.
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Melatonin has been demonstrated to play a variety of roles in plants. Of particular importance is its role as a potent antioxidative agent. In the present study, we generated melatonin-deficient tomato plants using virus-induced gene silencing (VIGS) approach and melatonin-rich tomato plants by foliar application of melatonin. These tomato plants were used to assess the effect of melatonin on chilling-induced oxidative stress and chilling-induced photosynthesis inhibition. We found that melatonin deficiency increased accumulation of reactive oxygen species (ROS) and aggravated lipid peroxidation in chilling-stressed tomato leaves, while exogenous application of melatonin had the opposite effect. Under chilling stress, melatonin-deficient tomato plants showed impaired antioxidant capacity as evidenced by lower activities of antioxidant enzymes and decreased rations of reduced glutathione (GSH)/oxidized glutathione (GSSG) and reduced ascorbate (AsA)/oxidized ascorbate (DHA), compared with melatonin-rich tomato plants. Furthermore, suppression of melatonin biosynthesis led to more photosynthesis inhibition under the chilling condition and compromised the capability of subsequent photosynthesis recovery in tomato plants. In addition, melatonin-deficient tomato plants displayed less activity of an important Calvin-Benson cycle enzyme sedoheptulose-1,7-bisphosphatase (SBPase) than melatonin-rich tomato plants under chilling stress. Collectively, our data indicate that melatonin is critical for antioxidant capacity and redox balance and is in favor of photosynthesis in tomato plants under chilling stress.