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Journal articles on the topic 'Adenoviruses'
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1
Niczyporuk, Jowita Samanta, Elżbieta Samorek-Salamonowicz, and Hanna Czekaj. "Occurrence of Adenovirus Field Strains in Birds Infected with Marek’S Disease Virus." Bulletin of the Veterinary Institute in Pulawy 56, no. 4 (December 1, 2012): 435–40. http://dx.doi.org/10.2478/v10213-012-0077-2.
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Abstract The strains of adenoviruses were isolated from 356 birds with clinical form of Marek’s disease and coinfection with adenoviruses. A hexon gene fragment coding loop L1 of adenovirus strains was sequenced and obtained data were analysed with BLAST, Geneious 5.3, and MEGA5 software by comparison with nucleotide sequences of reference strains of fowl adenoviruses (FAdV-1 - FadV-12), two turkey adenoviruses, and two goose adenovirus strains. On this basis, serotypes of adenovirus strains were determined. Sequences of all adenovirus strains isolated from birds infected with Marek’s disease virus were classified into six serotypes representing four species. Mostly FAdV-7, FAdV2/11, and FAdV-8a serotypes were found.
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Abbink, Peter, Lori F. Maxfield, David Ng'ang'a, Erica N. Borducchi, M. Justin Iampietro, Christine A. Bricault, Jeffrey E. Teigler, et al. "Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors." Journal of Virology 89, no. 3 (November 19, 2014): 1512–22. http://dx.doi.org/10.1128/jvi.02950-14.
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ABSTRACTAdenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.IMPORTANCEAlthough there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens.
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Moore, P. L., A. D. Steele, and J. J. Alexander. "Relevance of Commercial Diagnostic Tests to Detection of Enteric Adenovirus Infections in South Africa." Journal of Clinical Microbiology 38, no. 4 (2000): 1661–63. http://dx.doi.org/10.1128/jcm.38.4.1661-1663.2000.
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The prevalence of enteric adenoviruses detected by an in-house enzyme-linked immunosorbent assay (the RIVM-ELISA) ranged from 13 to 38%, and subgroup F adenoviruses comprised 86%. All subgroup F adenoviruses reacted with both RIVM anti-adenovirus type 40 (Ad40) and anti-adenovirus type 41 (Ad41) monoclonal antibodies but were not detected by Adenoclone Type 40/41 enzyme immunoassay (EIA). The correlation between the Biotrin EIA and RIVM-ELISA results was low (26%). Immunospecific tests suggest that a significant proportion of enteric adenoviruses, possibly comprising previously unidentified or emerging types, are not detected by commercial diagnostic tests in South Africa.
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Zhang, Wenli, Kemal Mese, Sebastian Schellhorn, Nora Bahlmann, Nicolas Mach, Oskar Bunz, Akshay Dhingra, et al. "High-Throughput Cloning and Characterization of Emerging Adenovirus Types 70, 73, 74, and 75." International Journal of Molecular Sciences 21, no. 17 (September 2, 2020): 6370. http://dx.doi.org/10.3390/ijms21176370.
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Recently an increasing number of new adenovirus types associated with type-dependent pathogenicity have been identified. However, identification of these clinical isolates represents the very first step to characterize novel pathogens. For deeper analyses, these adenoviruses need to be further characterized in basic virology experiments or they could be applied in translational research. To achieve this goal, it is essential to get genetic access and to enable genetic modification of these novel adenovirus genomes (deletion, insertion, and mutation). Here we demonstrate a high-throughput approach to get genetic access to new adenoviruses via homologous recombination. We first defined the cloning conditions regarding homology arm-length and input adenoviral genome amounts. Then we cloned four naturally occurring adenoviruses (Ad70, Ad73, Ad74, and Ad75) into easy-to-manipulate plasmids and genetically modified them by reporter gene insertion. Three recombinant adenoviruses (Ad70, Ad73, and Ad74) containing a reporter cassette were successfully reconstituted. These novel reporter-labeled adenoviruses were further characterized using the inserted luciferase reporter with respect to receptor usage, presence of anti-adenovirus antibodies, and tropism in vitro. The identified receptor usage, the relatively low prevalence of anti-adenovirus antibodies, and the various cancer cell line transduction pattern are important features of these new pathogens providing essential information for their therapeutic application.
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Maluquer de Motes, Carlos, Pilar Clemente-Casares, Ayalkibet Hundesa, Margarita Mart�n, and Rosina Girones. "Detection of Bovine and Porcine Adenoviruses for Tracing the Source of Fecal Contamination." Applied and Environmental Microbiology 70, no. 3 (March 2004): 1448–54. http://dx.doi.org/10.1128/aem.70.3.1448-1454.2004.
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ABSTRACT In this study, a molecular procedure for the detection of adenoviruses of animal origin was developed to evaluate the level of excretion of these viruses by swine and cattle and to design a test to facilitate the tracing of specific sources of environmental viral contamination. Two sets of oligonucleotides were designed, one to detect porcine adenoviruses and the other to detect bovine and ovine adenoviruses. The specificity of the assays was assessed in 31 fecal samples and 12 sewage samples that were collected monthly during a 1-year period. The data also provided information on the environmental prevalence of animal adenoviruses. Porcine adenoviruses were detected in 17 of 24 (70%) pools of swine samples studied, with most isolates being closely related to serotype 3. Bovine adenoviruses were present in 6 of 8 (75%) pools studied, with strains belonging to the genera Mastadenovirus and Atadenovirus and being similar to bovine adenoviruses of types 2, 4, and 7. These sets of primers produced negative results in nested PCR assays when human adenovirus controls and urban-sewage samples were tested. Likewise, the sets of primers previously designed for detection of human adenovirus also produced negative results with animal adenoviruses. These results indicate the importance of further studies to evaluate the usefulness of these tests to trace the source of fecal contamination in water and food and for environmental studies.
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Liu, Minli, Lefang Jiang, Weihua Cao, Jianguo Wu, and Xulin Chen. "Identification of Inhibitors and Drug Targets for Human Adenovirus Infections." Viruses 14, no. 5 (May 4, 2022): 959. http://dx.doi.org/10.3390/v14050959.
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Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.
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Dirven, Clemens M. F., Jacques Grill, Martine L. M. Lamfers, Paul van der Valk, Angelique M. Leonhart, Victor W. van Beusechem, Hidde J. Haisma, et al. "Gene therapy for meningioma: improved gene delivery with targeted adenoviruses." Journal of Neurosurgery 97, no. 2 (August 2002): 441–49. http://dx.doi.org/10.3171/jns.2002.97.2.0441.
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Object. Due to their surgical inaccessibility or aggressive behavior, some meningiomas cannot be cured with current treatment strategies. Gene therapy is an emerging strategy for the treatment of brain tumors, which the authors investigated to determine whether adenoviruses could be used for gene transfer in meningioma cells. Methods. The presence of the high-affinity Coxsackievirus and adenovirus receptor (CAR) for adenovirus type 5, as well as endothelial growth factor receptor (EGFR) and alphav integrins (ITGAVs), were analyzed in primary tumors by using immunohistochemical studies and in primary meningioma cell cultures by using fluorescence-activated cell sorting. Targeting of adenoviruses to EGFR was achieved using bispecific antibodies, whereas targeting of adenoviruses to the ITGAVs was accomplished by insertion of an RGD (arginine-glycine-aspartic acid) motif in the adenovirus fiber HI loop. Gene transfer efficiency of untargeted and targeted vectors was compared in primary cell cultures and in spheroids derived from patients' resected tumor material. The presence of CARs was observed in all tumors and in all but one of the derived primary meningioma cells. The higher expression of EGFRs and ITGAVs indicated that these receptors could be used as alternative targets to redirect the adenoviruses. Redirection of adenoviruses to the EGFRs or integrins enhanced gene transfer threefold (range two—sevenfold) for EGFRs in primary meningioma cells and ninefold (range three—23-fold) for integrins (p = 0.002, analysis of variance). The effect of adenovirus targeting was confirmed in spheroids composed of primary meningioma cells. Conclusions. Gene transfer with adenoviruses targeted to tumor-specific receptors is very effective in primary meningioma cells and spheroids. These vectors are promising agents for gene therapy of meningiomas.
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Segerman, Anna, John P. Atkinson, Marko Marttila, Veronica Dennerquist, Göran Wadell, and Niklas Arnberg. "Adenovirus Type 11 Uses CD46 as a Cellular Receptor." Journal of Virology 77, no. 17 (September 1, 2003): 9183–91. http://dx.doi.org/10.1128/jvi.77.17.9183-9191.2003.
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ABSTRACT The 51 human adenovirus serotypes are divided into six species (A to F). Many adenoviruses use the coxsackie-adenovirus receptor (CAR) for attachment to host cells in vitro. Species B adenoviruses do not compete with CAR-binding serotypes for binding to host cells, and it has been suggested that species B adenoviruses use a receptor other than CAR. Species B adenoviruses mainly cause disease in the respiratory tract, the eyes, and in the urinary tract. Here we demonstrate that adenovirus type 11 (Ad11; of species B) binds to Chinese hamster ovary (CHO) cells transfected with CD46 (membrane cofactor protein)-cDNA at least 10 times more strongly than to CHO cells transfected with cDNAs encoding CAR or CD55 (decay accelerating factor). Nonpermissive CHO cells were rendered permissive to Ad11 infection upon transfection with CD46-cDNA. Soluble Ad11 fiber knob but not Ad7 or Ad5 knob inhibited binding of Ad11 virions to CD46-transfected cells, and anti-CD46 antibodies inhibited both binding of and infection by Ad11. From these results we conclude that CD46 is a cellular receptor for Ad11.
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Hesse, Andrea, Daniela Kosmides, Roland E. Kontermann, and Dirk M. Nettelbeck. "Tropism Modification of Adenovirus Vectors by Peptide Ligand Insertion into Various Positions of the Adenovirus Serotype 41 Short-Fiber Knob Domain." Journal of Virology 81, no. 6 (December 27, 2006): 2688–99. http://dx.doi.org/10.1128/jvi.02722-06.
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ABSTRACT Recombinant adenoviruses have emerged as promising agents in therapeutic gene transfer, genetic vaccination, and viral oncolysis. Therapeutic applications of adenoviruses, however, would benefit substantially from targeted virus cell entry, for example, into cancer or immune cells, as opposed to the broad tropism that adenoviruses naturally possess. Such tropism modification of adenoviruses requires the deletion of their natural cell binding properties and the incorporation of cell binding ligands. The short fibers of subgroup F adenoviruses have recently been suggested as a tool for genetic adenovirus detargeting based on the reduced infectivity of corresponding adenovectors with chimeric fibers in vitro and in vivo. The goal of our study was to determine functional insertion sites for peptide ligands in the adenovirus serotype 41 (Ad41) short fiber knob. With a model peptide, CDCRGDCFC, we could demonstrate that ligand incorporation into three of five analyzed loops of the knob, namely, EG, HI, and IJ, is feasible without a loss of fiber trimerization. The resulting adenovectors showed enhanced infectivity for various cell types, which was superior to that of viruses with the same peptide fused to the fiber C terminus. Strategies to further augment gene transfer efficacy by extension of the fiber shaft, insertion of tandem copies of the ligand peptide, or extension of the ligand-flanking linkers failed, indicating that precise ligand positioning is pivotal. Our study establishes that internal ligand incorporation into a short-shafted adenovirus fiber is feasible and suggests the Ad41 short fiber with ligand insertion into the top (IJ loop) or side (EG and HI loops) of the knob domain as a novel platform for genetic targeting of therapeutic adenoviruses.
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Crenshaw, Brennetta J., Leandra B. Jones, Courtnee’ R. Bell, Sanjay Kumar, and Qiana L. Matthews. "Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy." Biomedicines 7, no. 3 (August 19, 2019): 61. http://dx.doi.org/10.3390/biomedicines7030061.
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Human adenoviruses are large (150 MDa) doubled-stranded DNA viruses that cause respiratory infections. These viruses are particularly pathogenic in healthy and immune-compromised individuals, and currently, no adenovirus vaccine is available for the general public. The purpose of this review is to describe (i) the epidemiology and pathogenicity of human adenoviruses, (ii) the biological role of adenovirus vectors in gene therapy applications, and (iii) the potential role of exosomes in adenoviral infections.
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Richardson, Ciarán, Paul Brennan, Martin Powell, Stuart Prince, Yun-Hsiang Chen, O. Brad Spiller, and Martin Rowe. "Susceptibility of B lymphocytes to adenovirus type 5 infection is dependent upon both coxsackie–adenovirus receptor and αvβ5 integrin expression." Journal of General Virology 86, no. 6 (June 1, 2005): 1669–79. http://dx.doi.org/10.1099/vir.0.80806-0.
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Human lymphocytes are resistant to genetic modification, particularly from recombinant adenoviruses, thus hampering the analysis of gene function using adenoviral vectors. This study engineered an Epstein–Barr virus-transformed B-lymphoblastoid cell line permissive to adenovirus infection and elucidated key roles for both the coxsackie–adenovirus receptor and αvβ5 integrin in mediating entry of adenoviruses into these cells. The work identified a strategy for engineering B cells to become susceptible to adenovirus infection and showed that such a strategy could be useful for the introduction of genes to alter lymphoblastoid-cell gene expression.
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Blanchette, Paola, and Jose G. Teodoro. "A Renaissance for Oncolytic Adenoviruses?" Viruses 15, no. 2 (January 26, 2023): 358. http://dx.doi.org/10.3390/v15020358.
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In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of “oncolytic viruses” has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, a genetically engineered herpesvirus, for the treatment of metastatic melanoma. Despite the slower progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Among all the clinical trials currently using viral oncolytic agents, the largest proportion of these are using recombinant adenovirus. Many trials are currently underway to use oncolytic virus in combination with immune checkpoint inhibitors (ICIs), and early results using oncolytic adenovirus in this manner are starting to show promise. Many of the existing strategies to engineer adenoviruses were designed to enhance selective tumor cell replication without much regard to interactions with the immune system. Adenovirus possesses a wide range of viral factors to attenuate both innate anti-viral pathways and immune cell killing. In this review, we summarize the strategies of oncolytic adenoviruses currently in clinical trials, and speculate how the mutational backgrounds of these viruses may impact upon the efficacy of these agents in oncolytic and immunotherapy. Despite decades of research on human adenoviruses, the interactions that these viruses have with the immune system remains one of the most understudied aspects of the virus and needs to be improved to rationally design the next generation of engineered viruses.
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Nwachuku, Nena, Charles P. Gerba, Amy Oswald, and Faezeh D. Mashadi. "Comparative Inactivation of Adenovirus Serotypes by UV Light Disinfection." Applied and Environmental Microbiology 71, no. 9 (September 2005): 5633–36. http://dx.doi.org/10.1128/aem.71.9.5633-5636.2005.
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ABSTRACT The results of this study confirm that adenoviruses are the most resistant enteric viruses to inactivation by UV light and that adenovirus 40 appears to be the most resistant. The effect of freeze-thawing and storage in water may affect the sensitivity of some adenoviruses to inactivation by UV light.
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Watanabe, Maki, Yuya Nishikawaji, Hirotaka Kawakami, and Ken-ichiro Kosai. "Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy." Viruses 13, no. 12 (December 14, 2021): 2502. http://dx.doi.org/10.3390/v13122502.
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Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse “CRAs that can specifically target tumors with multiple factors” (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.
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Nikitenko, N. A., T. Speiseder, E. Lam, P. M. Rubtsov, Kh D. Tonaeva, S. A. Borzenok, T. Dobner, and V. S. Prassolov. "Regulation of Human Adenovirus Replication by RNA Interference." Acta Naturae 7, no. 3 (September 15, 2015): 100–107. http://dx.doi.org/10.32607/20758251-2015-7-3-100-107.
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Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy.
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D. M. Teixeira, A. M. Rodrigues, R. S. Bandeira J. A. M. Siqueira, C. S. Júnior M. S. S. Lucena, L. S. Soares Y. B. Gabbay, and L. D. Silva. "Norovirus and Adenovirus Among Children from Public Day Care Centers in Brazil." International Journal of Current Microbiology and Applied Sciences 10, no. 9 (September 10, 2021): 431–40. http://dx.doi.org/10.20546/ijcmas.2021.1009.050.
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Introduction: Enteric viruses, including noroviruses and adenovirus are pathogens associated with outbreaks and sporadic cases of gastroenteritis in worldwide. This study aimed investigate cases of gastroenteritis caused by noroviruses and adenoviruses in children attending Public Daycare Centers in Brazil. Material and Methods: In this study, 135 fecal samples were examined using RT-PCR assays, sequencing and phylogenetic analysis. Results: The prevalence for norovirus and adenovirus was 13.3% (18/135) and 58.5% (79/135), respectively. Noroviruses were more frequent in symptomatic individuals (22.7%), whereas adenoviruses were more observed in asymptomatic children (61.8%). Three norovirus genotypes were detected (GII.P4, GII.P7, GII.P12) and adenovirus strains were classified into five species (A-F). The data revealed the dynamics of genotypic distribution of noroviruses and adenoviruses among children attending day care centers. The data indicated that symptomatic and asymptomatic children were infected with several strains of NoV e AdV. The additional evolutionary analyses need to be further investigated.
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Diakoudi, Georgia, Gianvito Lanave, Ana Moreno, Chiara Chiapponi, Enrica Sozzi, Alice Prosperi, Vittorio Larocca, et al. "Surveillance for Adenoviruses in Bats in Italy." Viruses 11, no. 6 (June 6, 2019): 523. http://dx.doi.org/10.3390/v11060523.
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Adenoviruses are important pathogens of humans and animals. Bats have been recognized as potential reservoirs of novel viruses, with some viruses being regarded as a possible zoonotic threat to humans. In this study, we report the detection and analysis of adenoviruses from different bat species in northern Italy. Upon sequence and phylogenetic analysis, based on a short diagnostic fragment of the highly-conserved DNA polymerase gene, we identified potential novel candidate adenovirus species, including an avian-like adenovirus strain. An adenovirus isolate was obtained in simian cell lines from the carcass of a Pipistrellus kuhlii, and the complete genome sequence was reconstructed using deep sequencing technologies. The virus displayed high nucleotide identity and virtually the same genome organization as the Pipistrellus pipistrellus strain PPV1, isolated in Germany in 2007. Gathering data on epidemiology and the genetic diversity of bat adenoviruses may be helpful to better understand their evolution in the mammalian and avian hosts.
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Wei, Qiang, Jiaming Fan, Junyi Liao, Yulong Zou, Dongzhe Song, Jianxiang Liu, Jing Cui, et al. "Engineering the Rapid Adenovirus Production and Amplification (RAPA) Cell Line to Expedite the Generation of Recombinant Adenoviruses." Cellular Physiology and Biochemistry 41, no. 6 (2017): 2383–98. http://dx.doi.org/10.1159/000475909.
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Background/Aims: While recombinant adenoviruses are among the most widely-used gene delivery vectors and usually propagated in HEK-293 cells, generating recombinant adenoviruses remains time-consuming and labor-intense. We sought to develop a rapid adenovirus production and amplification (RAPA) line by assessing human Ad5 genes (E1A, E1B19K/55K, pTP, DBP, and DNA Pol) and OCT1 for their contributions to adenovirus production. Methods: Stable transgene expression in 293T cells was accomplished by using piggyBac system. Transgene expression was determined by qPCR. Adenoviral production was assessed with titering, fluorescent markers and/or luciferase activity. Osteogenic activity was assessed by measuring alkaline phosphatase activity. Results: Overexpression of both E1A and pTP led to a significant increase in adenovirus amplification, whereas other transgene combinations did not significantly affect adenovirus amplification. When E1A and pTP were stably expressed in 293T cells, the resultant RAPA line showed high efficiency in adenovirus amplification and production. The produced AdBMP9 infected mesenchymal stem cells with highest efficiency and induced most effective osteogenic differentiation. Furthermore, adenovirus production efficiency in RAPA cells was dependent on the amount of transfected DNA. Under optimal transfection conditions high-titer adenoviruses were obtained within 5 days of transfection. Conclusion: The RAPA cells are highly efficient for adenovirus production and amplification.
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Kulanayake, Shermila, and Suresh K. Tikoo. "Adenovirus Core Proteins: Structure and Function." Viruses 13, no. 3 (February 28, 2021): 388. http://dx.doi.org/10.3390/v13030388.
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Adenoviruses have served as a model for investigating viral-cell interactions and discovering different cellular processes, such as RNA splicing and DNA replication. In addition, the development and evaluation of adenoviruses as the viral vectors for vaccination and gene therapy has led to detailed investigations about adenovirus biology, including the structure and function of the adenovirus encoded proteins. While the determination of the structure and function of the viral capsid proteins in adenovirus biology has been the subject of numerous reports, the last few years have seen increased interest in elucidating the structure and function of the adenovirus core proteins. Here, we provide a review of research about the structure and function of the adenovirus core proteins in adenovirus biology.
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Vermeulen, Christie, Tereza Brachtlova, Nikki Tol, Ida H. van der Meulen-Muileman, Jasmina Hodzic, Henri J. van de Vrugt, and Victor W. van Beusechem. "Evaluation of a Novel Oncolytic Adenovirus Silencing SYVN1." International Journal of Molecular Sciences 23, no. 23 (December 6, 2022): 15430. http://dx.doi.org/10.3390/ijms232315430.
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Oncolytic adenoviruses are promising new anticancer agents. To realize their full anticancer potential, they are being engineered to express therapeutic payloads. Tumor suppressor p53 function contributes to oncolytic adenovirus activity. Many cancer cells carry an intact TP53 gene but express p53 inhibitors that compromise p53 function. Therefore, we hypothesized that oncolytic adenoviruses could be made more effective by suppressing p53 inhibitors in selected cancer cells. To investigate this concept, we attenuated the expression of the established p53 inhibitor synoviolin (SYVN1) in A549 lung cancer cells by RNA interference. Silencing SYVN1 inhibited p53 degradation, thereby increasing p53 activity, and promoted adenovirus-induced A549 cell death. Based on these observations, we constructed a new oncolytic adenovirus that expresses a short hairpin RNA against SYVN1. This virus killed A549 cells more effectively in vitro and inhibited A549 xenograft tumor growth in vivo. Surprisingly, increased susceptibility to adenovirus-mediated cell killing by SYVN1 silencing was also observed in A549 TP53 knockout cells. Hence, while the mechanism of SYVN1-mediated inhibition of adenovirus replication is not fully understood, our results clearly show that RNA interference technology can be exploited to design more potent oncolytic adenoviruses.
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Jonsson, Mari I., Annasara E. Lenman, Lars Frängsmyr, Cecilia Nyberg, Mohamed Abdullahi, and Niklas Arnberg. "Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells." Journal of Virology 83, no. 8 (January 21, 2009): 3816–25. http://dx.doi.org/10.1128/jvi.02562-08.
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ABSTRACT Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.
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Sibanda, Timothy, and Anthony I. Okoh. "Assessment of the Incidence of Enteric Adenovirus Species and Serotypes in Surface Waters in the Eastern Cape Province of South Africa: Tyume River as a Case Study." Scientific World Journal 2012 (2012): 1–9. http://dx.doi.org/10.1100/2012/949216.
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TaqMan real-time PCR was used for the detection and quantitation of adenoviruses in Tyume River water samples over a 12-month period. A total of 72 samples were analysed, and 22 samples were positive for adenovirus. Of the positive samples, 18 were collected from downstream sampling points. Among the downstream sampling points, adenovirus detection rate increased with distance downstream, being 28%, 33%, and 39% for Alice, Drayini, and Manqulweni, respectively. The Alice sampling site had the highest concentrations of adenovirus ranging between6.54×103 genome copies/L and8.49×104 genome copies/L. The observed trend could have been expected considering the level of anthropogenic activities in areas along the lower stretch of Tyume River, with the major one being the effluent of treated and semi treated sewage from wastewater treatment facilities. Adenovirus detection was sporadic at most sampling sites. Multiplex conventional PCR was used for the detection of clinically important adenovirus species B, C, and F and their serotypes. Species C and F adenoviruses were detected in 77% and 18% of the samples, respectively. Most adenovirus positive samples were obtained from areas of increased population densities. The presence of adenoviruses may confirm the risk of its transmission to the human population.
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B, Tadesse. "Review on Adeno Virus; As a Vaccine Vehicle." Open Access Journal of Veterinary Science & Research 2, no. 3 (2017): 1–12. http://dx.doi.org/10.23880/oajvsr-16000138.
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Adenoviruses have moved to the forefront of vaccinology and are showing substantial prom ise as vehicles for antigen delivery for a number of vaccines currently being developed. Most studies to date have focused on human serotype adenoviruses, particularly human adenovirus type 5. Human serotype adenovirus vaccine vectors are particularly usef ul for development of veterinary vaccines as neutralizing antibodies to the vector will not usually be present in the vaccinates. Most vectors currently used as vaccine carriers are deleted in E1 gene. The original E1 deleted adenoviral vectors were constr ucted by homologous recombination. Replication incompetent vectors contain an antigen expression cassette substituted for the deleted E1A – E1B region. These replication incompitant adenoviruses can not replicate because of the deletion of the essential vir al E1 gene region containing two genes. Replication competent adenoviral vectors encode all of the remaining adenoviral antigens in addition to the transgene product, i.e., the vaccine antigen. The potential for adenoviruses to elicit powerful B cell and T cell responses in the mammalian host are the main reason for the use of these vectors in vaccine development. For effective veterinary use, extensive research on adenoviral vaccine vectors should be undertaken.
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Balagué, Cristina, Francisco Noya, Ramon Alemany, Louise T. Chow, and David T. Curiel. "Human Papillomavirus E6E7-Mediated Adenovirus Cell Killing: Selectivity of Mutant Adenovirus Replication in Organotypic Cultures of Human Keratinocytes." Journal of Virology 75, no. 16 (August 15, 2001): 7602–11. http://dx.doi.org/10.1128/jvi.75.16.7602-7611.2001.
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ABSTRACT Replication-competent adenoviruses are being investigated as potential anticancer agents. Exclusive virus replication in cancer cells has been proposed as a safety trait to be considered in the design of oncolytic adenoviruses. From this perspective, we have investigated several adenovirus mutants for their potential to conditionally replicate and promote the killing of cells expressing human papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high percentage of anogenital cancers. For this purpose, we have employed an organotypic model of human stratified squamous epithelium derived from primary keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We show that, whereas wild-type adenovirus promotes a widespread cytopathic effect in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins, shows no selectivity of replication as it efficiently kills all normal and E6E7-expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7-expressing cultures. We conclude that the organotypic keratinocyte culture represents a distinct model to evaluate adenovirus selectivity and that, based on this model, further modifications of the adenovirus genome are required to restrict adenovirus replication to tumor cells.
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Van Doornum, G. J. J., and J. C. De Jong. "Rapid Shell Vial Culture Technique for Detection of Enteroviruses and Adenoviruses in Fecal Specimens: Comparison with Conventional Virus Isolation Method." Journal of Clinical Microbiology 36, no. 10 (1998): 2865–68. http://dx.doi.org/10.1128/jcm.36.10.2865-2868.1998.
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Detection of enteroviruses and adenoviruses mainly in fecal specimens by rapid culture with inoculation onto cell monolayers in flat-bottom tubes by centrifugation and immunofluorescence staining with genus-specific monoclonal antibodies was compared with that by the conventional virus isolation procedure. For both conventional culture and shell vial culture human lung fibroblast cells and tertiary monkey kidney cells were used. For enterovirus detection, 979 clinical specimens (916 stool specimens, 56 cerebrospinal fluid specimens, and 7 nasopharyngeal swabs) were used. Conventional culture detected 74 enterovirus isolates. A cytopathic effect compatible with the presence of an enterovirus after 3 days of incubation occurred in 25 of the 74 (34%) specimens that eventually became positive. The detection rate for enteroviruses by rapid cell culture after 2 to 3 days of incubation was 42 of 74 (57%). The genus-specific enterovirus monoclonal antibody did not react with strains of echovirus types 22 and 23 or enterovirus type 71. Rapid cell culture for the detection of adenoviruses was performed with 567 clinical specimens (536 stool specimens, 25 cerebrospinal fluid specimens, and 6 miscellaneous specimens), in which 42 adenoviruses were found by conventional culture. Nine of the 42 (21%) adenovirus isolates were detected by conventional culture within 3 days after inoculation, whereas 21 (50%) were found by rapid cell culture within 2 to 3 days. Only two of the nine specimens found to be positive for the enteric adenovirus type 41 by conventional culture as well by a type-specific enzyme-linked immunosorbent assay (ELISA) tested positive by rapid cell culture. In conclusion, the rapid shell vial assay allows the early detection and identification of enteroviruses and adenoviruses in clinical specimens but is markedly less sensitive than the conventional isolation procedure according to the eventual results of the conventional isolation procedure. Conventional cell culture remains a prerequisite for serotyping of enteroviral isolates. On the basis of the results for adenovirus type 41, the rapid detection of adenoviruses was not considered to be useful for the detection of clinically relevant adenoviruses in fecal samples.
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Arafa, Amany A., Adel Abdel-Moneim, Rehab G. Khalil, Waled M. El-Senousy, Mahmoud M. Kamel, Dalia Y. Kadry, Gamal Allam, and Ahmed S. Abdel-Moneim. "Association between Pediatric Adenovirus Infection and Type 1 Diabetes." Children 9, no. 10 (September 29, 2022): 1494. http://dx.doi.org/10.3390/children9101494.
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Background: Viruses are among the inducers of type 1 diabetes (T1D) as they are implicated in the initiation of β-cell destruction. This study aimed to explore the link between adenoviruses’ infection, inflammatory biomarkers, and the development of T1D. Methods: The study population included 80 children with T1D and 40 healthy controls (2–16 years old). The T1D group was further clustered into two groups according to time of T1D diagnosis: a group of children who were diagnosed during the first year of life and a second group who were diagnosed after the first year of life. Adenovirus DNA, anti-adenovirus IgG, cytokines, and lipid profiles were screened in the different groups. The results were statistically assessed using one-way analysis of variance (ANOVA) and LSD t-test. Results: Positive adenovirus PCR was detected in 2.5% and 20% of normal and T1D children, respectively. Moreover, the positive PCR results for adenovirus were found significantly higher in the T1D group, who were diagnosed during the first year of life (33.4%), in comparison to those diagnosed after the first year of life (12%). Anti-adenoviruses IgG was found in 12.5% and 40% of healthy controls and diabetic children, respectively. Seropositive results were found to be higher in newly diagnosed children (46.7%) in comparison to those previously diagnosed with T1D (36%). Body mass index (BMI), IFN-γ, IL-15, adiponectin, lipid profile, and microalbuminuria were significantly increased in T1D adenoviruses-positive children compared to children who were negative for adenoviruses. Conclusions: Adenovirus infection could be among the contributing risk factors and may play a role in the induction of T1D in children.
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Park, Min ji, Su Kyung Lee, Hyun Soo Kim, and Jeong-Won Seo. "Adenoviral Keratoconjunctivitis in Korea: Serotypes and Clinical Characteristics." Annals of Optometry and Contact Lens 21, no. 4 (December 25, 2022): 150–55. http://dx.doi.org/10.52725/aocl.2022.21.4.150.
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Purpose: Human adenoviruses are a major cause of epidemic keratoconjunctivitis. Of over 60 genotypes, subgroup D is associated with epidemic keratoconjunctivitis. There are, however, no data regarding the genotypes of conjunctivitis-causing adenoviruses in Korea. The purpose of this study was to determine the types of adenoviruses causing epidemic keratoconjunctivitis and clinical manifestations in Korea.Methods: From November 2016 to September 2017, 20 conjunctival swab specimens were collected from patients who were clinically suspected to have adenoviral keratoconjunctivitis. Nucleic acids were extracted using a QIAamp Viral mini kit and processed on the QIAcube platform. Genotyping targeted for adenovirus capsid hexon genes was performed by using the polymerase chain reaction and sequencing techniques. Patient ages ranged from 18 days to 69 years (median, 37 years).Results: Of 20 collected specimens, 17 (85.0%) were genotyped. Three samples were not amplified with our primer sets. Eleven samples (64.7%) were adenovirus type 8, five (29.4%) were type 37, and one was type 64. All 17 genotyped patients showed conjunctival injections (100%) and follicles (100%), and 12 (84.6%) showed pseudomembrane formation. In case of patients genotyped type 8, most of them showed corneal manifestations and involvement of cornea by type 37 showed filamentary keratitis.Conclusions: This study showed that the polymerase chain reaction and direct sequencing for adenovirus hexon genes of conjunctival swab samples were effective techniques for genotyping the adenoviruses that cause epidemic keratoconjunctivitis. The most common causes of adenoviral keratoconjunctivitis in Korea were adenovirus types 8 and 37 in this period of time. Conjunctival injection, follicle formation, and pseudomembrane formation were the major manifestations of adenovirus types 8 and 37 infections.
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Harrach, B. "Reptile Adenoviruses in Cattle?" Acta Veterinaria Hungarica 48, no. 4 (December 2000): 485–90. http://dx.doi.org/10.1556/004.48.2000.4.11.
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This paper describes a hypothesis on the origin of the members of the recently established adenovirus genus, Atadenovirus, invading cattle, sheep, deer, duck and poultry. Comparison of the phylogenetic trees of adenoviruses and their hosts suggests a very ancient but common origin for the atadenoviruses. The surprisingly large difference between these virus types and other adenoviruses infecting the same host can be easily understood by assuming their separate evolution in different hosts (e.g., in reptiles versus a coevolution with mammals and birds, respectively) followed by a later host switch.
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Athukorala, Ajani, Karla J. Helbig, Brian P. Mcsharry, Jade K. Forwood, and Subir Sarker. "Adenoviruses in Avian Hosts: Recent Discoveries Shed New Light on Adenovirus Diversity and Evolution." Viruses 14, no. 8 (August 13, 2022): 1767. http://dx.doi.org/10.3390/v14081767.
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While adenoviruses cause infections in a wide range of vertebrates, members of the genus Atadenovirus, Siadenovirus, and Aviadenovirus predominantly infect avian hosts. Several recent studies on avian adenoviruses have encouraged us to re-visit previously proposed adenovirus evolutionary concepts. Complete genomes and partial DNA polymerase sequences of avian adenoviruses were extracted from NCBI and analysed using various software. Genomic analyses and constructed phylogenetic trees identified the atadenovirus origin from an Australian native passerine bird in contrast to the previously established reptilian origin. In addition, we demonstrated that the theories on higher AT content in atadenoviruses are no longer accurate and cannot be considered as a species demarcation criterion for the genus Atadenovirus. Phylogenetic reconstruction further emphasised the need to reconsider siadenovirus origin, and we recommend extended studies on avian adenoviruses in wild birds to provide finer evolutionary resolution.
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Pring-Åkerblom, Patricia, Albert Heim, and F. E. John Trijssenaar. "Molecular Characterization of Hemagglutination Domains on the Fibers of Subgenus D Adenoviruses." Journal of Virology 72, no. 3 (March 1, 1998): 2297–304. http://dx.doi.org/10.1128/jvi.72.3.2297-2304.1998.
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ABSTRACT The adenovirus fiber mediates the agglutination of erythrocytes. Based on differential hemagglutinating properties, subgenus D adenoviruses can be subdivided into clusters DI, DII, and DIII. While subgenus DI adenoviruses agglutinate rat and human erythrocytes, DII adenoviruses simply agglutinate rat erythrocytes and DIII adenoviruses display no or only weak rat erythrocyte agglutination. Amino acid sequence comparisons revealed distinct domains on the fiber knob which could be involved in hemagglutination. In order to localize and characterize the domains responsible for the interaction with rat and human erythrocytes, potential hemagglutination domains of the adenovirus type 9 (Ad9) (subgenus DI) fiber knob were introduced into Ad17 (subgenus DII) and Ad28 (subgenus DIII) fiber knobs by primer-directed mutagenesis. Furthermore, rat erythrocyte hemagglutination domains were also introduced into the Ad3 (subgenus B) fiber knob, which only agglutinated monkey erythrocytes. Altogether, 27 chimeric and mutated fiber proteins were expressed in Escherichia coli and subsequently tested for hemagglutination activity. The hemagglutination tests revealed that at least two domains can mediate the agglutination of rat erythrocytes. While one domain is located on the GH loop, the other domain extends from the C β strand to the CD loop. The domain on the GH loop was partially conserved in all adenoviruses showing an incomplete hemagglutination pattern with rat erythrocytes. The domains involved in the agglutination of human erythrocytes are located on the CD and HI loops of the subgenus DI fiber knob.
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Rajaiya, Jaya, Amrita Saha, Ashrafali M. Ismail, Xiaohong Zhou, Ting Su, and James Chodosh. "Adenovirus and the Cornea: More Than Meets the Eye." Viruses 13, no. 2 (February 13, 2021): 293. http://dx.doi.org/10.3390/v13020293.
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Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.
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Tsoukas, Raphael L., Wolfram Volkwein, Jian Gao, Maren Schiwon, Nora Bahlmann, Thomas Dittmar, Claudia Hagedorn, et al. "A Human In Vitro Model to Study Adenoviral Receptors and Virus Cell Interactions." Cells 11, no. 5 (March 1, 2022): 841. http://dx.doi.org/10.3390/cells11050841.
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To develop adenoviral cell- or tissue-specific gene delivery, understanding of the infection mechanisms of adenoviruses is crucial. Several adenoviral attachment proteins such as CD46, CAR and sialic acid have been identified and studied. However, most receptor studies were performed on non-human cells. Combining our reporter gene-tagged adenovirus library with an in vitro human gene knockout model, we performed a systematic analysis of receptor usage comparing different adenoviruses side-by-side. The CRISPR/Cas9 system was used to knockout CD46 and CAR in the human lung epithelial carcinoma cell line A549. Knockout cells were infected with 22 luciferase-expressing adenoviruses derived from adenovirus species B, C, D and E. HAdV-B16, -B21 and -B50 from species B1 as well as HAdV-B34 and -B35 were found to be CD46-dependent. HAdV-C5 and HAdV-E4 from species E were found to be CAR-dependent. Regarding cell entry of HAdV-B3 and -B14 and all species D viruses, both CAR and CD46 play a role, and here, other receptors or attachment structures may also be important since transductions were reduced but not completely inhibited. The established human knockout cell model enables the identification of the most applicable adenovirus types for gene therapy and to further understand adenovirus infection biology.
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Hierholzer, J. C. "Adenoviruses in the immunocompromised host." Clinical Microbiology Reviews 5, no. 3 (July 1992): 262–74. http://dx.doi.org/10.1128/cmr.5.3.262.
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Adenoviruses are among the many pathogens and opportunistic agents that cause serious infection in the congenitally immunocompromised, in patients undergoing immunosuppressive treatment for organ and tissue transplants and for cancers, and in human immunodeficiency virus-infected patients. Adenovirus infections in these patients tend to become disseminated and severe, and the serotypes involved are clustered according to the age of the patient and the nature of the immunosuppression. Over 300 adenovirus infections in immunocompromised patients, with an overall case fatality rate of 48%, are reviewed in this paper. Children with severe combined immunodeficiency syndrome and other primary immunodeficiencies are exposed to the serotypes of subgroups B and C that commonly infect young children, and thus their infections are due to types 1 to 7 and 31 of subgenus A. Children with bone marrow and liver transplants often have lung and liver adenovirus infections that are due to an expanded set of subgenus A, B, C, and E serotypes. Adults with kidney transplants have viruses of subgenus B, mostly types 11, 34, and 35, which cause cystitis. This review indicates that 11% of transplant recipients become infected with adenoviruses, with case fatality rates from 60% for bone marrow transplant patients to 18% for renal transplant patients. Patients with AIDS become infected with a diversity of serotypes of all subgenera because their adult age and life-style expose them to many adenoviruses, possibly resulting in antigenically intermediate strains that are not found elsewhere. Interestingly, isolates from the urine of AIDS patients are generally of subgenus B and comprise types 11, 21, 34, 35, and intermediate strains of these types, whereas isolates from stool are of subgenus D and comprise many rare, new, and intermediate strains that are untypeable for practical purposes. It has been estimated that adenoviruses cause active infection in 12% of AIDS patients and that 45% of these infections terminate in death within 2 months. In all immunocompromised patients, generalized illness involving the central nervous system, respiratory system, hepatitis, and gastroenteritis usually have a fulminant course and result in death. Treatments for adenovirus infections are of little proven value, although certain purine and pyrimidine analogs have shown beneficial effects in vitro and may be promising drugs.
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Abdulqader Y. Hamad. "Antigenic and Molecular Detection of Adenoviruses from Sewage Water in Diyala Province – Iraq." Academic Science Journal 2, no. 2 (April 29, 2024): 20–30. http://dx.doi.org/10.24237/asj.02.02.703a.
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Waterborne viral illnesses are still have public health in both developed and developing. Adenovirus one of the enteroviruses are widely circulated in the environment even in the absence of associated clinical conditions in the community. Adenoviruses are the second cause of gastroenteritis after rotavirus. as they are responsible for 5-9 % of gastroenteritis cases in children. The objectives of study antigenic and molecular detection of adenovirus from water samples collected from sewage water plants (SWP) and draining canals (DC) in Diyala city (Iraq). This study was conducted in Diyala province for the period from January 2022 to August 2022. A total of 50 water samples were collected from sewage water plants and draining canals in plastic containers Immunochromatographic Assay (ICA) technique was used for direct detection of adenoviruses antigens a for molecular detection, the water samples were firstly ultra – centrifuged and the then viral nucleic acid (NA) of adenovirus were extracted Polymerase Chain Reaction (PCR) adenoviruses RNAs concentration were measured. (Sacace Biotechnologies PCR kit) technique was used for viral NAs detection, analysis was done using the statistical packages for social science version (27) and P value was considered significant. The Result using the Immunochromatographic Assay (ICA) The total positivity rate of adenovirus in sewage water plants and draining canals 18 (36%), while the Polymerase Chain Reaction (PCR) technique found that the total positivity rate was 29 (58%). The high detection rate of adenoviruses found in sewage water plants and draining canals by both immunological and molecular techniques may reflect the high prevalence of the virus in the community and recreating the risks public health deterioration.
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Needle, David B., Annabel G. Wise, Christopher R. Gregory, Roger K. Maes, Inga F. Sidor, Branson W. Ritchie, and Dalen Agnew. "Necrotizing Ventriculitis in Fledgling Chimney Swifts (Chaetura Pelagica) Associated With a Novel Adenovirus, Chimney Swift Adenovirus-1 (CsAdV-1)." Veterinary Pathology 56, no. 6 (July 22, 2019): 907–14. http://dx.doi.org/10.1177/0300985819861717.
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Five chimney swift fledglings died following a progressive loss of appetite and condition while being cared for by an experienced wildlife rehabilitator. All animals had severe necrotizing and heterophilic ventriculitis, with myriad epithelial cells characterized by karyomegaly with intranuclear inclusion bodies. Transmission electron microscopy showed distention of epithelial cell nuclei and chromatin peripheralization by nonenveloped, icosahedral, 75- to 85-nm-diameter virions. Degenerate nested PCR for a highly conserved region of the adenovirus DNA polymerase gene was positive. BLAST analysis of the amplicon sequence indicated the presence of a novel adenovirus, with 74% homology to Antarctic penguin adenoviruses and 72% homology to a bat adenovirus, at low query coverages of only 65% and 63%, respectively. BLAST analysis of the predicted amino acid sequence generated the highest scores for squamate adenoviruses at 100% query coverage. Based on phylogenetic analysis of the partial amino acid sequence of the DNA polymerase, the chimney swift virus was a novel adenovirus most closely related to the Atadenovirus genus. Using a probe based on the novel viral sequence, DNA in situ hybridization identified viral nucleic acid in the nucleus. While the tentatively named chimney swift adenovirus-1 (CsAdV-1) is so far classified with the Atadenoviruses, it is relatively divergent from other members of that genus and may represent the first identified member of a new genus of Adenoviruses.
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Jiang, Sunny C., Jijun Han, Jian-Wen He, and Weiping Chu. "Evaluation of four cell lines for assay of infectious adenoviruses in water samples." Journal of Water and Health 7, no. 4 (July 1, 2009): 650–56. http://dx.doi.org/10.2166/wh.2009.088.
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Human viral contamination in drinking and recreational waters poses health risks. The application of PCR-based molecular technology has advanced our knowledge of the occurrence and prevalence of human viruses in water; however, it has provided no information on viral viability and infectivity. Four human cell lines were compared for their sensitivity to different serotypes of human adenoviruses using the TCID50 test. The sensitivity of each cell line varied with different serotypes of adenovirus. Human embryonic kidney cell line 293A and human lung carcinoma cell line A549 were the most sensitive, especially to enteric adenovirus 40 and 41. Plaque assay of primary sewage samples showed 293A can detect viral plaques in 7 of 13 primary sewage samples tested. Adenoviruses were also isolated using 293A from environmental water concentrates. Cloning and sequencing of environmental adenoviral isolates indentified them to be aligned with adenoviruses serotype 40 and serotype 5. The result of this study suggests that plaque assay with 293A cell line is suitable for detection of adenovirus in the aquatic environment. Combining this cell culture with molecular methods for viral assay in the aquatic environment will provide critical information for risk assessment.
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Sato-Dahlman, Mizuho, Christopher J. LaRocca, Chikako Yanagiba, and Masato Yamamoto. "Adenovirus and Immunotherapy: Advancing Cancer Treatment by Combination." Cancers 12, no. 5 (May 21, 2020): 1295. http://dx.doi.org/10.3390/cancers12051295.
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Gene therapy with viral vectors has significantly advanced in the past few decades, with adenovirus being one of the most commonly employed vectors for cancer gene therapy. Adenovirus vectors can be divided into 2 groups: (1) replication-deficient viruses; and (2) replication-competent, oncolytic (OVs) viruses. Replication-deficient adenoviruses have been explored as vaccine carriers and gene therapy vectors. Oncolytic adenoviruses are designed to selectively target, replicate, and directly destroy cancer cells. Additionally, virus-mediated cell lysis releases tumor antigens and induces local inflammation (e.g., immunogenic cell death), which contributes significantly to the reversal of local immune suppression and development of antitumor immune responses (“cold” tumor into “hot” tumor). There is a growing body of evidence suggesting that the host immune response may provide a critical boost for the efficacy of oncolytic virotherapy. Additionally, genetic engineering of oncolytic viruses allows local expression of immune therapeutics, thereby reducing related toxicities. Therefore, the combination of oncolytic virus and immunotherapy is an attractive therapeutic strategy for cancer treatment. In this review, we focus on adenovirus-based vectors and discuss recent progress in combination therapy of adenoviruses with immunotherapy in preclinical and clinical studies.
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Gallardo, José, Marta Pérez-Illana, Natalia Martín-González, and Carmen San Martín. "Adenovirus Structure: What Is New?" International Journal of Molecular Sciences 22, no. 10 (May 15, 2021): 5240. http://dx.doi.org/10.3390/ijms22105240.
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Adenoviruses are large (~950 Å) and complex non-enveloped, dsDNA icosahedral viruses. They have a pseudo-T = 25 triangulation number with at least 12 different proteins composing the virion. These include the major and minor capsid proteins, core proteins, maturation protease, terminal protein, and packaging machinery. Although adenoviruses have been studied for more than 60 years, deciphering their architecture has presented a challenge for structural biology techniques. An outstanding event was the first near-atomic resolution structure of human adenovirus type 5 (HAdV-C5), solved by cryo-electron microscopy (cryo-EM) in 2010. Discovery of new adenovirus types, together with methodological advances in structural biology techniques, in particular cryo-EM, has lately produced a considerable amount of new, high-resolution data on the organization of adenoviruses belonging to different species. In spite of these advances, the organization of the non-icosahedral core is still a great unknown. Nevertheless, alternative techniques such as atomic force microscopy (AFM) are providing interesting glimpses on the role of the core proteins in genome condensation and virion stability. Here we summarize the current knowledge on adenovirus structure, with an emphasis on high-resolution structures obtained since 2010.
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Kovács, Gábor M., Andrew J. Davison, Alexender N. Zakhartchouk, and Balázs Harrach. "Analysis of the first complete genome sequence of an Old World monkey adenovirus reveals a lineage distinct from the six human adenovirus species." Journal of General Virology 85, no. 10 (October 1, 2004): 2799–807. http://dx.doi.org/10.1099/vir.0.80225-0.
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Simian adenovirus 3 (SAdV-3) is one of several adenoviruses that were isolated decades ago from Old World monkeys. Determination of the complete DNA sequence of SAdV-3 permitted the first full genomic comparison of a monkey adenovirus with adenoviruses of humans (HAdVs) and chimpanzees, which are recognized formally as constituting six of the species (HAdV-A to HAdV-F) within the genus Mastadenovirus. The SAdV-3 genome is 34 246 bp in size and has a G+C content of 55·3 mol%. It contains all the genes that are characteristic of the genus Mastadenovirus and has a single VA-RNA gene and six genes in each of the E3 and E4 regions. The genetic organization is the same as that of HAdV-12, a member of the HAdV-A species. Phylogenetic analyses showed that although SAdV-3 is related marginally more closely to HAdV-A and HAdV-F than to other species, it represents a unique lineage that branched at an early stage of primate adenovirus divergence. The results imply that the genetic layout in SAdV-3 and HAdV-12 may also have characterized the common ancestor of all sequenced primate adenoviruses.
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Tabrizi, Sepehr N., Alison E. Ling, Catriona S. Bradshaw, Christopher K. Fairley, and Suzanne M. Garland. "Human adenoviruses types associated with non-gonococcal urethritis." Sexual Health 4, no. 1 (2007): 41. http://dx.doi.org/10.1071/sh06054.
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Background: Role of adenoviruses in non-gonococcal urethritis (NGU) has been reported in only a few studies. The aim of the study was to detect and type adenoviruses in men presenting with NGU. Methods: 636 heterosexual and homosexual men presenting with NGU from Melbourne, Australia were recently evaluated for various aetiological organisms including adenovirus. We utilised methods including polymerase chain reaction for detection followed by sequence analysis to type positive samples. Results: Overall, 12 samples from patients with NGU had adenovirus detected. Five types were identified: type 4 (subgenus E), type 35 (subgenus B), and types 9, 37 and 49 (subgenus D). The presence of mixed adenovirus strains was not detected in any sample. Conclusion: Overall, subgenus B, D and E were predominant in this patient population.
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Echavarría, Marcela. "Adenoviruses in Immunocompromised Hosts." Clinical Microbiology Reviews 21, no. 4 (October 2008): 704–15. http://dx.doi.org/10.1128/cmr.00052-07.
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SUMMARY The number of patients with acquired immunodeficiency has grown steadily as a result of both a larger number of patients receiving solid organ and hematopoietic stem cell transplants and their longer survival times. The use of newer, more potent immunosuppressive regimens has increased the frequency of severe adenovirus infections. Human adenoviruses are a large group of viruses, represented by at least 52 serotypes with various genotypes divided into genomic clusters, and these may cause a broad variety of clinical manifestations. The development of molecular methods has increased the sensitivity and rapidity of adenovirus infection diagnosis. The implementation of PCR assays has significantly contributed to the identification of patients with disseminated adenovirus disease. More recently, the development of real-time PCR assays has permitted virus quantification and patient follow-up. There is no treatment for adenovirus with demonstrated efficacy, although cidofovir is widely used. Sensitive diagnostic tests for adenovirus can contribute to the early diagnosis and successful treatment of life-threatening adenovirus infections, especially in complex immunocompromised patients. The development of improved adenovirus therapy still remains a challenge. Adenovirus genetic diversity should be considered for diagnosis, typing, and therapeutic interventions.
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Lejeune, Noémie, Sarah Mathieu, Alexandra Decloux, Florian Poulain, Zoé Blockx, Kyle A. Raymond, Kévin Willemart, Jean-Pierre Vartanian, Rodolphe Suspène, and Nicolas A. Gillet. "The APOBEC3B cytidine deaminase is an adenovirus restriction factor." PLOS Pathogens 19, no. 2 (February 6, 2023): e1011156. http://dx.doi.org/10.1371/journal.ppat.1011156.
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Human adenoviruses (HAdVs) are a large family of DNA viruses counting more than a hundred strains divided into seven species (A to G). HAdVs induce respiratory tract infections, gastroenteritis and conjunctivitis. APOBEC3B is a cytidine deaminase that restricts several DNA viruses. APOBEC3B is also implicated in numerous cancers where it is responsible for the introduction of clustered mutations into the cellular genome. In this study, we demonstrate that APOBEC3B is an adenovirus restriction factor acting through a deaminase-dependent mechanism. APOBEC3B introduces C-to-T clustered mutations into the adenovirus genome. APOBEC3B reduces the propagation of adenoviruses by limiting viral genome replication, progression to late phase, and production of infectious virions. APOBEC3B restriction efficiency varies between adenoviral strains, the A12 strain being more sensitive to APOBEC3B than the B3 or C2 strains. In A12-infected cells, APOBEC3B clusters in the viral replication centers. Importantly, we show that adenovirus infection leads to a reduction of the quantity and/or enzymatic activity of the APOBEC3B protein depending on the strains. The A12 strain seems less able to resist APOBEC3B than the B3 or C2 strains, a characteristic which could explain the strong depletion of the APOBEC3-targeted motifs in the A12 genome. These findings suggest that adenoviruses evolved different mechanisms to antagonize APOBEC3B. Elucidating these mechanisms could benefit the design of cancer treatments. This study also identifies adenoviruses as triggers of the APOBEC3B-mediated innate response. The involvement of certain adenoviral strains in the genesis of the APOBEC3 mutational signature observed in tumors deserves further study.
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Choi, Samuel, and Sunny C. Jiang. "Real-Time PCR Quantification of Human Adenoviruses in Urban Rivers Indicates Genome Prevalence but Low Infectivity." Applied and Environmental Microbiology 71, no. 11 (November 2005): 7426–33. http://dx.doi.org/10.1128/aem.71.11.7426-7433.2005.
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ABSTRACT Real-time PCR was applied to quantify the abundance of human adenoviruses in two southern California urban rivers, the San Gabriel and Los Angeles. A total of 114 river samples from five different locations were collected over a 1-year period and analyzed for human adenoviruses, along with fecal indicator bacteria and coliphages. Adenoviruses were detected by real-time PCR in ∼16% of the samples, with concentrations ranging from 102 to 104 genomes per liter. However, a plaque assay using two human tissue culture cell lines, HEK-293A and A549, yielded negative results, suggesting that adenoviruses detected by real-time PCR are likely noninfectious. Enterovirus genome was detected in ∼7% of the samples by reverse transcription-PCR. Analysis by Spearman's rho rank order correlation showed significant correlations between fecal indicator bacteria and indicator virus (total coliform, fecal coliform, enterococcus, and coliphage values). However, no significant correlations were found between human adenoviruses quantified by real-time PCR and culturable coliphages or fecal indicator bacteria. Kruskal-Wallis chi-square analysis showed significant seasonal variability of all fecal indicator bacteria and coliphages, while no significant variability was observed for adenoviruses or enteroviruses. This study presents the first quantitative measurement of human adenovirus genomes in urban rivers and their statistical relationship to fecal indicator bacteria and coliphages. The uncoupling between high-number genome copies of adenoviruses detected by real-time PCR and the absence of infectivity detected by tissue culture suggests that genome-based detection methods are inadequate for direct assessment of human health risk.
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Kudryashova, A. M., A. G. Galstian, E. B. Faizuloev, A. Yu Olenin, G. V. Lisichkin, V. V. Zverev, and O. V. Borisova. "DETECTION OF ADENOVIRUS ANTIGEN BY A SURFACE-ENHANCED RAMAN SCATTERING ENZYME-LINKED IMMUNOSORBENT ASSAY." Journal of microbiology epidemiology immunobiology 1, no. 3 (August 25, 2019): 25–31. http://dx.doi.org/10.36233/0372-9311-2018-3-25-31.
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Aim. Study of the possibility of adenovirus antigen detection by recording of surface-enhanced Raman scattering (SERS) spectra of enzyme oxidized product of 3,3',5,5'-tetramethylbenzidine. Materials and methods. Clinical fecal samples containing adenoviruses, group A rotaviruses, noroviruses and healthy children samples, as well as laboratory strains of adenoviruses with a titer of 5 — 6 lg TCD50/ml were used. Sandwich immunoassay was used, the Raman spectra were recorded by a Raman spectrometer (532 nm) after incubation with silver nanoparticles. Results. The concordance of the adenovirus detection results was obtained in comparison with the enzyme immunoassay method with colorimetric detection and PCR. Conclusion. The possibility of TMB+ using as a SERS reporter and silver nanoparticles as a SERS substrate for the detection of adenovirus antigen in complex biological samples was shown.
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Arcangeletti, Maria-Cristina, Diego Germini, Davide Martorana, Isabella Rodighiero, Flora De Conto, Maria-Cristina Medici, Carlo Chezzi, and Adriana Calderaro. "High frequency of cultivable human subgroup F adenoviruses in stool samples from a paediatric population admitted to hospital with acute gastroenteritis." Journal of Medical Microbiology 63, no. 6 (June 1, 2014): 812–18. http://dx.doi.org/10.1099/jmm.0.072413-0.
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The family Adenoviridae consists of five genera of which the genus Mastadenovirus includes human viruses classified into 57 serotypes clustered into seven subgroups (A–G). Serotypes 40 and 41 (subgroup F) are specifically associated with childhood gastroenteritis and are the most common cause of acute gastroenteritis in young children after rotaviruses and noroviruses. Standard methods for laboratory diagnosis of adenovirus infection include electron microscopy (EM) and conventional cell culture (CCC), although it is widely considered that adenoviruses 40 and 41 are difficult to cultivate, such that their circulation is most likely underestimated. One hundred and ten faecal specimens from paediatric patients with gastroenteritis were confirmed positive for adenovirus by EM and/or CCC at the Virology Unit of the University Hospital of Parma, Italy, during the period January 2010–December 2012. They were analysed to determine the actual prevalence of adenovirus 40 and 41 in these patients using PCR and restriction endonuclease analysis, and to evaluate their ability to be cultivated in standard cell lines. The results showed a high prevalence of subgroup F (62.7 %), with serotype 41 (89.8 %) predominating over serotype 40 (10.2 %). Surprisingly, among the 75 adenoviruses isolated by CCC, 37 (49 %) belonged to subgroup F, suggesting a higher capacity of adenovirus 40 and 41 to replicate in cell culture than previously thought. PCR and restriction enzyme techniques provide an efficient means of diagnosing enteric adenoviruses correctly, including subgroup F adenovirus strains in young children with gastroenteritis.
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Sherwood, Victoria, Elizabeth King, Sabine Tötemeyer, Ian Connerton, and Kenneth H. Mellits. "Interferon treatment suppresses enteric adenovirus infection in a model gastrointestinal cell-culture system." Journal of General Virology 93, no. 3 (March 1, 2012): 618–23. http://dx.doi.org/10.1099/vir.0.037556-0.
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Exposure to interferon results in the rapid transcriptional induction of genes, many of which function to create an antiviral environment in potential host cells. For the majority of adenoviruses, replication is unaffected by the actions of interferon. It has previously been shown, using non-gastrointestinal cells, that the species F human adenoviruses are sensitive to the action of interferon. Here, we have developed an enterocyte-like cell-culture model to re-evaluate this question, and determined the effects of interferon on species F adenovirus during infection of gastrointestinal cells. We show that species F adenovirus type 40 is sensitive to the effects of interferon in gastrointestinal-like cells, which may help to explain its fastidious growth in culture.
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Zelenskiy, Yu R., M. S. Volkov, I. A. Komarov, N. V. Moroz, N. S. Mudrak, and T. V. Zhbanova. "Avian adenovirus infections: diversity of pathogens, hazard to poultry industry and problems of immunoprophylaxis (review)." Veterinary Science Today 13, no. 1 (March 15, 2024): 36–43. http://dx.doi.org/10.29326/2304-196x-2024-13-1-36-43.
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The data on diversity of adenovirus pathogens in nature and the role of the main representatives of the Adenoviridae family in poultry infectious pathology are presented. Special attention is paid to problematic issues of immunoprophylaxis due to lack of cross-immunity between different virus serotypes. There is no single and effective approach in the global strategy of immunoprophylaxis of avian adenoviruses, therefore, improving the means of avian adenovirus disease control is an urgent and important task. Avian adenovirus infections are represented by different nosological units: egg drop syndrome, hydropericardium syndrome, adenoviral gizzard erosion, marbled spleen disease of pheasants, hemorrhagic enteritis of turkeys, inclusion body hepatitis and many unclassified diseases. The paper provides data on the main nosological forms of adenovirus infections that pose a threat to cost-effective poultry farming, and highlights test results obtained by foreign authors on the effectiveness of some vaccines against adenovirus infection. Most vaccines have been developed to prevent avian hydropericardium syndrome, however, occurrence of many virus serotypes requires effective means of prevention and diagnosis in order to control other infections caused by adenoviruses. There is no registered vaccine against adenovirus infections that cause inclusion body hepatitis and adenoviral gizzard erosion. At the same time, inclusion body hepatitis alone accounts for 2.9% of all recorded avian infectious diseases. Vaccines registered in the Russian Federation are not enough to fully control these infections, and that requires a timely solution to the problem. The variety of avian adenoviruses determines the problems of their differential diagnosis and specific prevention.
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Purkayastha, Anjan, Susan E. Ditty, Jing Su, John McGraw, Ted L. Hadfield, Clark Tibbetts, and Donald Seto. "Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development." Journal of Virology 79, no. 4 (February 15, 2005): 2559–72. http://dx.doi.org/10.1128/jvi.79.4.2559-2572.2005.
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ABSTRACT Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253 ). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD.
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Denning, D., S. Bennett, T. Mullen, C. Moyer, D. Vorselen, G. J. L. Wuite, G. Nemerow, and W. H. Roos. "Maturation of adenovirus primes the protein nano-shell for successful endosomal escape." Nanoscale 11, no. 9 (2019): 4015–24. http://dx.doi.org/10.1039/c8nr10182e.
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He, Jian-Wen, and Sunny Jiang. "Quantification of Enterococci and Human Adenoviruses in Environmental Samples by Real-Time PCR." Applied and Environmental Microbiology 71, no. 5 (May 2005): 2250–55. http://dx.doi.org/10.1128/aem.71.5.2250-2255.2005.
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ABSTRACT Pathogenic bacteria and enteric viruses can be introduced into the environment via human waste discharge. Methods for rapid detection and quantification of human viruses and fecal indicator bacteria in water are urgently needed to prevent human exposure to pathogens through drinking and recreational waters. Here we describe the development of two real-time PCR methods to detect and quantify human adenoviruses and enterococci in environmental waters. For real-time quantification of enterococci, a set of primers and a probe targeting the 23S rRNA gene were used. The standard curve generated using Enterococcus faecalis genomic DNA was linear over a 7-log-dilution series. Serial dilutions of E. faecalis suspensions resulted in a lower limit of detection (LLD) of 5 CFU/reaction. To develop real-time PCR for adenoviruses, degenerate primers and a Taqman probe targeting a 163-bp region of the adenovirus hexon gene were designed to specifically amplify 14 different serotypes of human adenoviruses, including enteric adenovirus serotype 40 and 41. The standard curve generated was linear over a 5-log-dilution series, and the LLD was 100 PFU/reaction using serial dilutions of purified adenoviral particles of serotype 40. Both methods were optimized to be applicable to environmental samples. The real-time PCR methods showed a greater sensitivity in detection of adenoviruses in sewage samples than the viral plaque assay and in detection of enterococci in coastal waters than the bacterial culture method. However, enterococcus real-time PCR overestimated the number of bacteria in chlorinated sewage in comparison with the bacterial culture method. Overall, the ability via real-time PCR to detect enterococci and adenoviruses rapidly and quantitatively in the various environmental samples represents a considerable advancement and a great potential for environmental applications.