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Journal articles on the topic 'Viral antigen'
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1
Doan, Thu A., Johnathon Schafer, Erin D. Lucas, and Beth Tamburini. "Antigen archiving promotes secondary CD8+ T cell memory responses during an unrelated infection." Journal of Immunology 206, no. 1_Supplement (May 1, 2021): 102.06. http://dx.doi.org/10.4049/jimmunol.206.supp.102.06.
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Abstract Numerous studies have shown viral antigens can persist in lymph nodes after resolution of the infection. We showed that lymphatic endothelial cells (LECs), which comprise the lymphatic vasculature necessary for antigen drainage from the tissue, is the predominant cell type required for the persistence of antigen within the lymph node. We termed this process antigen archiving due the ability of LECs to actively archive antigens to which an immune response has occurred. This process involves antigen acquisition, retention, and exchange of the antigen between LECs and dendritic cells (DC), resulting in presentation of the archived antigens to CD8+ memory T cells and improving effector function. In more recent data, we demonstrated that LEC death causes the release of archived antigens during LN contraction. The objective of this study was to determine if during a secondary unrelated infection whether LEC death would occur and cause archived antigens to be released. As expected, we found that a second and unrelated viral infection causes LEC death within two to three weeks following infection. Within the same time frame that we observed LEC death, we observed a significant increase in archived antigen-specific endogenous memory T cells. This increase only occurred in mice that received an unrelated viral infection and not in those mice that did not receive the unrelated viral infection. In conclusion, archived antigen release during a secondary unrelated infection potentially boosts the archived antigen specific memory CD8+ T cell population. Understanding the mechanism of antigen release during multiple infections could ultimately lead to better strategies for vaccination and improve our understanding of how LECs influence immunity.
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Reignat, Stephanie, George J. M. Webster, David Brown, Graham S. Ogg, Abigail King, Suranjith L. Seneviratne, Geoff Dusheiko, Roger Williams, Mala K. Maini, and Antonio Bertoletti. "Escaping High Viral Load Exhaustion." Journal of Experimental Medicine 195, no. 9 (May 6, 2002): 1089–101. http://dx.doi.org/10.1084/jem.20011723.
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Deletion, anergy, and a spectrum of functional impairments can affect virus-specific CD8 cells in chronic viral infections. Here we characterize a low frequency population of CD8 cells present in chronic hepatitis B virus (HBV) infection which survive in the face of a high quantity of viral antigen. Although they do not appear to exert immunological pressure in vivo, these CD8 cells are not classically “tolerant” since they proliferate, lyse, and produce antiviral cytokines in vitro. They are characterized by altered HLA/peptide tetramer reactivity, which is not explained by TCR down-regulation or reduced functional avidity and which can be reversed with repetitive stimulation. CD8 cells with altered tetramer binding appear to have a specificity restricted to envelope antigen and not to other HBV antigens, suggesting that mechanisms of CD8 cell dysfunction are differentially regulated according to the antigenic form and presentation of individual viral antigens.
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Tewalt, Eric Franklin, Jean M. Grant, Erica L. Granger, Keri B. Donohue, and Chris C. Norbury. "Viral Sequestration of Antigen Subverts Cross Priming (93.14)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S168. http://dx.doi.org/10.4049/jimmunol.178.supp.93.14.
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Abstract Antigens driven by poxvirus late promoters are produced in much larger quantities than those driven by early promoters both in vitro and in vivo. Despite the abundance of protein produced, antigens driven by late poxvirus promoters typically induce a low or undetectable CD8+ T cell response following immunization in vivo, while those driven by early promoters induce a significant response. We show that antigen driven by late promoters is not expressed in primary dendritic cells, preventing induction of naïve CD8+ T cells via the direct presentation pathway. However, it is puzzling why the cross priming pathway does not compensate for this lack of direct presentation as the relevance of the pathway is based upon its ability to induce CD8+ T cells in the absence of viral infection of DC or upon the expression of viral modulatory molecules that may prevent direct presentation. Our studies demonstrate that when present in similar quantities, late promoter driven antigen is not available for cross priming in vivo. In contrast, cellular antigen from virus-infected cells can access the cross priming pathway under comparable conditions. The mechanism involved does not require the shutoff of host cell protein synthesis but is due to the sequestration of late promoter driven antigen in viral factories inhibiting antigen donation to DC. This observation indicates a novel mechanism of viral evasion, whereby antigen is not available for use in either the direct or cross priming pathways.
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Ramakrishnan, Kamna, and Darren R. Flower. "Discriminating antigen and non-antigen using proteome dissimilarity II: viral and fungal antigens." Bioinformation 5, no. 1 (June 24, 2010): 35–38. http://dx.doi.org/10.6026/97320630005035.
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Antonuk, A., O. Dyshkant, and O. Nikitin. "ВИЗНАЧЕННЯ ТЕРМІНУ ЗБЕРІГАННЯ ТА СТАБІЛЬНОСТІ ІНФЕКЦІЙНОЇ АКТИВНОСТІ КУЛЬТУРАЛЬНИХ АНТИГЕНІВ ШТАМУ ГВК 1 Ж ТА КЛОНУ ГВК 2 ТТ ДЛЯ ПОСТАНОВКИ РДП." Scientific Messenger of LNU of Veterinary Medicine and Biotechnology 18, no. 3(70) (September 4, 2016): 8–13. http://dx.doi.org/10.15421/nvlvet7002.
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Getting a culture herpesviridae antigens first and second types is possible using cell cultures inoculated epithelial pig testicles and tracheal calf respectively. The incubation herpesviridae first and second types should be conducted on the above lines in cell culture incubator at a temperature of 37,5 °C for up to 10 days. To maximize the release of virus from cell culture fluid viral after incubation need three frozen at temperatures from –18 °C to + 20 °C. The resulting liquid is purified viral the culture by centrifugation. Determining the infectious activity of the culture liquid viral performed in response hemagglutination of horse erythrocytes suspension, and the material is titrated to 1: 128 in the two recurrence. Accounting reaction was performed at 2, 4, 6 and 8 hours. Infectious material volumetric activity was 1:4. Getting antigens envisages concentrating liquid viral culture fluid by reverse dialysis. To do this, conducted a study to identify the optimal concentration of antigen suitable for setting reaction diffusion precipitation. At 1:10 antigen concentration result of different reactions, depending on the account of the diffusion precipitation reactions. When concentration of EHV–1 antigen was found that the optimum dilution for its RDP is 1:20. In assessing the EHV–2 antigen, found that suitable for setting reaction diffusion precipitation RDP is an antigen concentrated from 1:60 to 1:20. In practical terms, most rational use of antigen, concentrated 20 times.Keeping culture antigens can be conducted frozen at minus 18 ° C, for 12 months because after six months of storage of the frozen infectious activity was not decreased. And in research in 12 months noted a line of precipitation in native samples and serum diluted 1:2. Working antigens for diffuse precipitation reaction must be sterile on various forms of bacteria and fungi. Therefore, samples of viral antigens were plated on agar culture media for general purpose (plain agar), after having spent preserving antigen using 0.01% solution mertiolyatu rate of 0.1 sm3/1sm3 culture fluid. Using such an environment can detect material in the test organisms belonging to different morphological groups. Research sterility subjected to viral antigens, herpesviridae infection on the first type of herpesviridae infection and the second type.
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Storset, A. K., Ø. Evensen, and E. Rimstad. "Immunohistochemical Identification of Caprine Arthritis-Encephalitis Virus in Paraffin-embedded Specimens from Naturally Infected Goats." Veterinary Pathology 34, no. 3 (May 1997): 180–88. http://dx.doi.org/10.1177/030098589703400302.
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The expression of caprine arthritis-encephalitis virus capsid protein was studied in seropositive naturally infected asymptomatic goats (10), seropositive naturally infected encephalitic kids (12) and goats (4), and noninfected control goats (3). Rabbit antiserum to recombinant viral capsid and matrix proteins were used in a biotin-streptavidin-alkaline phosphatase complex immunohistochemical method on sections of formalin-and ethanol-fixed tissue specimens. Macrophages in inflamed areas of the lung (8/12), in the brain (5/16), and in the spinal cord (4/16) from encephalitic animals harbored viral antigens, as revealed by immunohistochemistry and use of a capsid protein-specific antiserum. Altogether 12/16 encephalitic animals tested positive for viral antigen. Viral antigens were found in 5/10 seropositive asymptomatic goats in macrophages located in the lung (3), the udder (1), and the medulla of lymph nodes (4). None of the control animals tested positive for viral antigen. Ethanol fixation showed highest sensitivity, and the lowest antigen concentration that revealed a positive signal discernible from background was twofold higher in ethanol-fixed specimens than in formalin-fixed specimens. The evaluation was performed on artificial antigen substrates embedded with defined concentrations of recombinant viral capsid protein. Immunohistochemistry is a valuable supplement to the methods presently available for diagnosis in cases suspicious of caprine arthritis-encephalitis.
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O'REILLY, DAVID R., ALLAN M. CRAWFORD, and LOIS K. MILLER. "Viral proliferating cell nuclear antigen." Nature 337, no. 6208 (February 1989): 606. http://dx.doi.org/10.1038/337606a0.
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Woodland, David L. "Viral Inhibition of Antigen Presentation." Viral Immunology 29, no. 7 (September 2016): 377–78. http://dx.doi.org/10.1089/vim.2016.29011.dlw.
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Miller, Daniel M., and Daniel D. Sedmak. "Viral effects on antigen processing." Current Opinion in Immunology 11, no. 1 (February 1999): 94–99. http://dx.doi.org/10.1016/s0952-7915(99)80017-x.
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Yewdell, Jonathan W., and Ann B. Hill. "Viral interference with antigen presentation." Nature Immunology 3, no. 11 (November 2002): 1019–25. http://dx.doi.org/10.1038/ni1102-1019.
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Sullivan, Christopher S., and James M. Pipas. "T Antigens of Simian Virus 40: Molecular Chaperones for Viral Replication and Tumorigenesis." Microbiology and Molecular Biology Reviews 66, no. 2 (June 2002): 179–202. http://dx.doi.org/10.1128/mmbr.66.2.179-202.2002.
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SUMMARY Simian virus 40 (SV40) is a small DNA tumor virus that has been extensively characterized due to its relatively simple genetic organization and the ease with which its genome is manipulated. The large and small tumor antigens (T antigens) are the major regulatory proteins encoded by SV40. Large T antigen is responsible for both viral and cellular transcriptional regulation, virion assembly, viral DNA replication, and alteration of the cell cycle. Deciphering how a single protein can perform such numerous and diverse functions has remained elusive. Recently it was established that the SV40 T antigens, including large T antigen, are molecular chaperones, each with a functioning DnaJ domain. The molecular chaperones were originally identified as bacterial genes essential for bacteriophage growth and have since been shown to be conserved in eukaryotes, participating in an array of both viral and cellular processes. This review discusses the mechanisms of DnaJ/Hsc70 interactions and how they are used by T antigen to control viral replication and tumorigenesis. The use of the DnaJ/Hsc70 system by SV40 and other viruses suggests an important role for these molecular chaperones in the regulation of the mammalian cell cycle and sheds light on the enigmatic SV40 T antigen—a most amazing molecule.
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Mathews, Anila A. "Role of NS1 Antigen in the Diagnosis of Dengue Viral Infection." Journal of Communicable Diseases 49, no. 04 (January 3, 2018): 52–55. http://dx.doi.org/10.24321/0019.5138.201734.
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Ayinde, Diana, Timothée Bruel, Sylvain Cardinaud, Françoise Porrot, Julia G. Prado, Arnaud Moris, and Olivier Schwartz. "SAMHD1 Limits HIV-1 Antigen Presentation by Monocyte-Derived Dendritic Cells." Journal of Virology 89, no. 14 (April 29, 2015): 6994–7006. http://dx.doi.org/10.1128/jvi.00069-15.
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ABSTRACTMonocyte-derived dendritic cells (MDDC) stimulate CD8+cytotoxic T lymphocytes (CTL) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class I (MHC-I) molecules. MDDC are poorly susceptible to HIV-1, in part due to the presence of SAMHD1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dNTPs) and degrades viral RNA. Vpx, an HIV-2/SIVsm protein absent from HIV-1, antagonizes SAMHD1 by inducing its degradation. The impact of SAMHD1 on the adaptive cellular immune response remains poorly characterized. Here, we asked whether SAMHD1 modulates MHC-I-restricted HIV-1 antigen presentation. Untreated MDDC or MDDC pretreated with Vpx were exposed to HIV-1, and antigen presentation was examined by monitoring the activation of an HIV-1 Gag-specific CTL clone. SAMHD1 depletion strongly enhanced productive infection of MDDC as well as endogenous HIV-1 antigen presentation. Time-lapse microscopy analysis demonstrated that in the absence of SAMHD1, the CTL rapidly killed infected MDDC. We also report that various transmitted/founder (T/F) HIV-1 strains poorly infected MDDC and, as a consequence, did not stimulate CTL. Vesicular stomatitis virus glycoprotein (VSV-G) pseudotyping of T/F alleviated a block in viral entry and induced antigen presentation only in the absence of SAMHD1. Furthermore, by using another CTL clone that mostly recognizes incoming HIV-1 antigens, we demonstrate that SAMHD1 does not influence exogenous viral antigen presentation. Altogether, our results demonstrate that the antiviral activity of SAMHD1 impacts antigen presentation by DC, highlighting the link that exists between restriction factors and adaptive immune responses.IMPORTANCEUpon viral infection, DC may present antigens derived from incoming viral material in the absence of productive infection of DC or from newly synthesized viral proteins. In the case of HIV, productive infection of DC is blocked at an early postentry step. This is due to the presence of SAMHD1, a cellular enzyme that depletes intracellular levels of dNTPs and inhibits viral reverse transcription. We show that the depletion of SAMHD1 in DCs strongly stimulates the presentation of viral antigens derived from newly produced viral proteins, leading to the activation of HIV-1-specific cytotoxic T lymphocytes (CTL). We further show in real time that the enhanced activation of CTL leads to killing of infected DCs. Our results indicate that the antiviral activity of SAMHD1 not only impacts HIV replication but also impacts antigen presentation by DC. They highlight the link that exists between restriction factors and adaptive immune responses.
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Fleischer, B., H. Becht, and R. Rott. "Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones." Journal of Immunology 135, no. 4 (October 1, 1985): 2800–2804. http://dx.doi.org/10.4049/jimmunol.135.4.2800.
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Abstract The nature of the viral antigens recognized by influenza A virus-immune cytotoxic T lymphocytes (CTL) is still a matter of debate. We have used four human influenza A virus-specific T lymphocyte clones with antigen-specific cytotoxic and proliferative activity to investigate the requirements for recognition of viral antigens on infected cells. One clone recognized a cross-reactive determinant on the viral hemagglutinin, and two clones were specific for different epitopes on the viral nucleoprotein (NP). A fourth clone seemed to be specific for the viral M protein. Target cell recognition was abrogated by the addition, during infection, of the lysosomotropic drug chloroquine, known to inhibit antigen processing. Furthermore, target cells that had been pulsed with soluble purified NP were recognized and were lysed by the NP-specific clone. This reaction could also be abrogated by the addition of chloroquine during pulsing. These results were obtained irrespective of whether EBV-transformed B lymphoblastoid cells or Ia antigen-expressing T cell blasts were used as target cells. It is concluded that CTL can recognize internal viral proteins that are actively presented at the surface of the target cell. These data indicate that probably every viral protein can function as a target molecule for virus-immune CTL.
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Hirano, Minato, Kentaro Yoshii, Mizuki Sakai, Rie Hasebe, Osamu Ichii, and Hiroaki Kariwa. "Tick-borne flaviviruses alter membrane structure and replicate in dendrites of primary mouse neuronal cultures." Journal of General Virology 95, no. 4 (April 1, 2014): 849–61. http://dx.doi.org/10.1099/vir.0.061432-0.
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Neurological diseases caused by encephalitic flaviviruses are severe and associated with high levels of mortality. However, detailed mechanisms of viral replication in the brain and features of viral pathogenesis remain poorly understood. We carried out a comparative analysis of replication of neurotropic flaviviruses: West Nile virus, Japanese encephalitis virus and tick-borne encephalitis virus (TBEV), in primary cultures of mouse brain neurons. All the flaviviruses multiplied well in primary neuronal cultures from the hippocampus, cerebral cortex and cerebellum. The distribution of viral-specific antigen in the neurons varied: TBEV infection induced accumulation of viral antigen in the neuronal dendrites to a greater extent than infection with other viruses. Viral structural proteins, non-structural proteins and dsRNA were detected in regions in which viral antigens accumulated in dendrites after TBEV replication. Replication of a TBEV replicon after infection with virus-like particles of TBEV also induced antigen accumulation, indicating that accumulated viral antigen was the result of viral RNA replication. Furthermore, electron microscopy confirmed that TBEV replication induced characteristic ultrastructural membrane alterations in the neurites: newly formed laminal membrane structures containing virion-like structures. This is the first report describing viral replication in and ultrastructural alterations of neuronal dendrites, which may cause neuronal dysfunction. These findings encourage further work aimed at understanding the molecular mechanisms of viral replication in the brain and the pathogenicity of neurotropic flaviviruses.
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Kang, Bora, Su Jeong Ryu, and Eun Young Choi. "CD8 T cell response for H60 requires CD4 T cell help when the antigen is expressed as a viral antigen (132.36)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 132.36. http://dx.doi.org/10.4049/jimmunol.184.supp.132.36.
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Abstract CD4 helper T cell is critical for the generation of primary and memory CD8 T cells specific for non-inflammatory antigens. Minor histocompatibility antigens are representative non-inflammatory cellular antigens that require CD4 help for the response induction, and we have shown that CD8 T cell response for minor histocompatibility antigen H60 is dependent on CD4 help not only for the primary response but also for the secondary response inductions. In this study, we addressed a question whether H60 epitope as a viral antigen would require CD4 help for specific response induction. A recombinant vaccinia virus expressing H60-CD8 epitope and HY-CD4 epitope (rVV-H60HY) was used for immunization of B6 female mice. Immunization with the recombinant virus induced a significant amount of H60-specific CD8 T cell proliferation with a peak frequency around 10~20% of total blood CD8 T cells. The response was CD4 help dependent both after the primary and secondary viral challenges. The CD4 help could be substituted by combined treatment of TLR agonists and anti-CD40 antibody. Our results demonstrate that CD4 help is required for appropriate CD8 T cell responses specific for H60 not only as cellular antigen but also as viral antigen, and the signaling through TLR and CD40 would license antigen presenting cells to appropriately activate antigen-specific CD8 T cells.
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López, Daniel, Olga Calero, Mercedes Jiménez, Margarita García-Calvo, and Margarita Del Val. "Antigen Processing of a Short Viral Antigen by Proteasomes." Journal of Biological Chemistry 281, no. 41 (July 21, 2006): 30315–18. http://dx.doi.org/10.1074/jbc.m605973200.
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Menne, Stephan, Carol A. Roneker, Brent E. Korba, John L. Gerin, Bud C. Tennant, and Paul J. Cote. "Immunization with Surface Antigen Vaccine Alone and after Treatment with 1-(2-Fluoro-5-Methyl-β-l-Arabinofuranosyl)-Uracil (l-FMAU) Breaks Humoral and Cell-Mediated Immune Tolerance in Chronic Woodchuck Hepatitis Virus Infection." Journal of Virology 76, no. 11 (June 1, 2002): 5305–14. http://dx.doi.org/10.1128/jvi.76.11.5305-5314.2002.
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ABSTRACT Woodchucks chronically infected with the woodchuck hepatitis virus (WHV) were treated with the antiviral drug 1-(2-fluoro-5-methyl-β-l-arabinofuranosyl)-uracil (l-FMAU) or placebo for 32 weeks. Half the woodchucks in each group then received four injections of surface antigen vaccine during the next 16 weeks. Vaccination alone elicited a low-level antibody response to surface antigen in most carriers but did not affect serum WHV DNA and surface antigen. Carriers treated first with l-FMAU to reduce serum WHV DNA and surface antigen and then vaccinated had a similar low-level antibody response to surface antigen. Following vaccinations, cell-mediated immunity to surface antigen was demonstrated in both groups, independent of serum viral and antigen load, but was significantly enhanced in woodchucks treated with l-FMAU and was broadened to include other viral antigens (core, e, and x antigens and selected core peptides). Cell-mediated immunity and antibody responses to surface antigen were observed after drug discontinuation in half of the carriers that received l-FMAU alone. Surface antigen vaccine alone or in combination with drug broke humoral and cell-mediated immune tolerance in chronic WHV infection, but the combination with drug was more effective. This suggested that a high viral and antigen load in carriers is important in maintaining immunologic tolerance during chronicity. The humoral and cellular immunity associated with the combination of l-FMAU and vaccine resembled that observed in self-limited WHV infection. Such combination therapy represents a potentially useful approach to the control of chronic hepatitis B virus infection in humans.
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White, Harry N. "B-Cell Memory Responses to Variant Viral Antigens." Viruses 13, no. 4 (March 26, 2021): 565. http://dx.doi.org/10.3390/v13040565.
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A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection. In conflict with this process is the ability that many viruses have to mutate their antigens to escape infection- or vaccine-induced antibody memory responses. Mutable viruses such as dengue virus, influenza virus and of course coronavirus have a major global health impact, exacerbated by this ability to evade immune responses through mutation. There have been several outstanding recent studies on B-cell memory that also shed light on the potential and limitations of antibody memory to protect against viral antigen variation, and so promise to inform new strategies for vaccine design. For the purposes of this review, the current understanding of the different memory B-cell (MBC) populations, and their potential to recognize mutant antigens, will be described prior to some examples from antibody responses against the highly mutable RNA based flaviviruses, influenza virus and SARS-CoV-2.
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Conly, JM, and BL Johnston. "Ode to Oseltamivir and Amantadine?" Canadian Journal of Infectious Diseases and Medical Microbiology 17, no. 1 (2006): 11–14. http://dx.doi.org/10.1155/2006/106989.
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Influenza A and B viruses are the two major types of influenza viruses that cause human epidemic disease. Influenza A viruses are further categorized into subtypes based on two surface antigens: hemagglutinin (H) and neuraminidase (N). Influenza B viruses are not categorized into subtypes (1). Influenza A viruses are found in many animal species, including humans, ducks, chickens, pigs, whales, horses and seals, whereas influenza B viruses circulate only among humans. The H antigen contains common and strain-specific antigens, demonstrates antigenic variation, and acts as a site of attachment of the virus to host cells to initiate infection (1). The N antigen contains subtype-specific antigens and also demonstrates antigenic variation between subtypes. It is a surface glycoprotein possessing enzymatic activity essential for viral replication in both influenza A and B viruses. The N antigen allows the release of newly produced virions from infected host cells, prevents the formation of viral aggregates after release from the host cells, and prevents viral inactivation by respiratory mucous (2,3). It is thought that this enzyme may also promote viral penetration into respiratory epithelial cells and may contribute to the pathogenicity of the virus by promoting production of proinflammatory cytokines such as interleukin-1 and tumour necrosis factor from macrophages (4-6).
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Moens, Ugo, and Andrew Macdonald. "Effect of the Large and Small T-Antigens of Human Polyomaviruses on Signaling Pathways." International Journal of Molecular Sciences 20, no. 16 (August 12, 2019): 3914. http://dx.doi.org/10.3390/ijms20163914.
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Viruses are intracellular parasites that require a permissive host cell to express the viral genome and to produce new progeny virus particles. However, not all viral infections are productive and some viruses can induce carcinogenesis. Irrespective of the type of infection (productive or neoplastic), viruses hijack the host cell machinery to permit optimal viral replication or to transform the infected cell into a tumor cell. One mechanism viruses employ to reprogram the host cell is through interference with signaling pathways. Polyomaviruses are naked, double-stranded DNA viruses whose genome encodes the regulatory proteins large T-antigen and small t-antigen, and structural proteins that form the capsid. The large T-antigens and small t-antigens can interfere with several host signaling pathways. In this case, we review the interplay between the large T-antigens and small t-antigens with host signaling pathways and the biological consequences of these interactions.
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Vigouroux, Stéphane, Eric Yvon, Hans-Joachim Wagner, Ettore Biagi, Gianpietro Dotti, Uluhan Sili, Cecilia Lira, Cliona M. Rooney, and Malcolm K. Brenner. "Induction of Antigen-Specific Regulatory T Cells following Overexpression of a Notch Ligand by Human B Lymphocytes." Journal of Virology 77, no. 20 (October 15, 2003): 10872–80. http://dx.doi.org/10.1128/jvi.77.20.10872-10880.2003.
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ABSTRACT In mice, activation of the Notch pathway in T cells by antigen-presenting cells overexpressing Notch ligands favors differentiation of regulatory T lymphocytes responsible for antigen-specific tolerance. To determine whether this mechanism operates in human T cells, we used Epstein-Barr virus-positive lymphoblastoid cell lines (EBV-LCL) as our (viral) antigen-presenting cells and overexpressed the Notch ligand Jagged-1 (EBV-LCL J1) by adenoviral transduction. The EBV-LCL J1s were cocultured with autologous T cells, and the proliferative and cytotoxic responses to EBV antigens were measured. Transduction had no effect on EBV-LCL expression of major histocompatibility complex (MHC) antigens or of costimulatory molecules CD80, CD86, and CD40. However, we observed a 35% inhibition of proliferation and a >65% reduction in cytotoxic-T-cell activity, and interleukin 10 production was increased ninefold. These EBV-LCL J1-stimulated T lymphocytes act as antigen-specific regulatory cells, since their addition to fresh autologous T cells cultured with autologous nontransduced EBV-LCL cells significantly inhibited both proliferation and cytotoxic effector function. Within the inhibitory population, CD4+CD25+ and CD8+CD25− T cells had the greatest activity. This inhibition appears to be antigen-specific, since responses to Candida and cytomegalovirus antigens were unaffected. Hence, transgenic expression of Jagged-1 by antigen-presenting cells can induce antigen-specific regulatory T cells in humans and modify immune responses to viral antigens.
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Fernandez, A., M. Hewicker, G. Trautwein, J. Pohlenz, and B. Liess. "Viral Antigen Distribution in the Central Nervous System of Cattle Persistently Infected with Bovine Viral Diarrhea Virus." Veterinary Pathology 26, no. 1 (January 1989): 26–32. http://dx.doi.org/10.1177/030098588902600105.
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Distribution of viral antigens in the central nervous system of 25 cattle with a persistent bovine viral diarrhea virus (BVDV) infection was studied. Using a polyclonal antiserum produced in pigs and the direct immunofluorescence and immunoperoxidase technique, BVDV antigen was located exclusively in neurons. Predilection sites for viral persistence were cerebral cortex and hippocampus; in other areas of brain and spinal cord, viral antigens were in single neurons or small groups of neurons. There was no morphological evidence of cellular alteration due to viral persistence. Perivascular lymphocytic infiltrations were in affected nervous tissue. It is concluded that the central nervous system is an important location for persistence of BVDV.
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Johansson, Bert E., and Manon M. J. Cox. "Influenza viral neuraminidase: the forgotten antigen." Expert Review of Vaccines 10, no. 12 (December 2011): 1683–95. http://dx.doi.org/10.1586/erv.11.130.
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Grandien, Monica. "Viral diagnosis by antigen detection techniques." Clinical and Diagnostic Virology 5, no. 2-3 (May 1996): 81–90. http://dx.doi.org/10.1016/0928-0197(96)00209-7.
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Doan, Thu A., and Beth Tamburini. "Archived antigen boosts CD8 T cell memory responses during an unrelated infection." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 110.18. http://dx.doi.org/10.4049/jimmunol.208.supp.110.18.
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Abstract Numerous studies have shown viral antigens can persist in lymph nodes after the resolution of the infection. We showed that lymphatic endothelial cells (LECs), which comprise the lymphatic vasculature, are the predominant cell type required for the persistence of antigen within the lymph node. We termed this process antigen archiving due to the ability of LECs to actively acquire and store antigens to which an active immune response occurred. This process involves antigen acquisition, retention, and exchange of the antigen between LECs and dendritic cells, resulting in the presentation of the archived antigens to CD8 memory T cells and improving effector function. In more recent data, we demonstrated that LEC death causes the release of archived antigens during LN contraction. We found that archived antigens could be released during an unrelated viral infection, during the time frame of LEC death. This release of antigen was visualized by a significant increase in archived antigen-specific endogenous or transferred memory CD8 T cells, but not memory T cells of an unrelated specificity. The increase in archived antigen-specific CD8 T cells maintained a more effector-like phenotype and performed significantly better upon antigenic challenge with Listeria monocytogenes (LM) expressing ovalbumin. Mice that received an unrelated infection 2–3 weeks prior to antigenic challenge demonstrated improved protection against LM-ova. In conclusion, archived antigen release during a secondary unrelated infection boosts the archived antigen-specific memory CD8 T cell population. These findings bring into question whether some previous data demonstrating heterologous immunity may be a result of archived antigen release. Supported by R01 AI121209 R21 AI155929
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Kolawole, Elizabeth Motunrayo, and Brian D. Evavold. "Omega-3 rich diet alters T cell affinity and decreases anti-viral immunity." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 148.13. http://dx.doi.org/10.4049/jimmunol.196.supp.148.13.
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Abstract There has been much investigation into the influence of dietary fatty acids with regard to modulation of immune function. Omega-3 polyunsaturated fatty acids have been shown to exert beneficial anti-inflammatory effects for both chronic and acute inflammatory disease. Acute viral infection can be controlled and eliminated with an effective CD8 response. Despite studies suggesting the incorporation of omega-3 fatty acids into lipid membranes leading to the production of less inflammatory metabolites, little is known about T cell engagement with peptide-MHC (pMHC) antigen and whether omega-3 fatty acids modulate T cell responses. Here using the novel two dimensional (2D) micropipette adhesion frequency assay we determine T cell frequency and affinity for antigen on a single cell basis. Our data indicates that dietary fish oil reduces antigen affinity in T cell receptor transgenic cells. Moreover, we demonstrate decreased polyclonal numbers of antigen specific (gp-33) T cells at peak anti viral immunity to lymphocytic choriomeningitis (LCMV) infection. These data indicate that omega-3 fatty acids decrease antigen recognition to viral antigens.
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Zhao, Xiaorong, Ramiro J. Madden-Fuentes, Becky X. Lou, James M. Pipas, Jeannine Gerhardt, Christopher J. Rigell, and Ellen Fanning. "Ataxia Telangiectasia-Mutated Damage-Signaling Kinase- and Proteasome-Dependent Destruction of Mre11-Rad50-Nbs1 Subunits in Simian Virus 40-Infected Primate Cells." Journal of Virology 82, no. 11 (March 19, 2008): 5316–28. http://dx.doi.org/10.1128/jvi.02677-07.
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ABSTRACT Although the mechanism of simian virus 40 (SV40) DNA replication has been extensively investigated with cell extracts, viral DNA replication in productively infected cells utilizes additional viral and host functions whose interplay remains poorly understood. We show here that in SV40-infected primate cells, the activated ataxia telangiectasia-mutated (ATM) damage-signaling kinase, γ-H2AX, and Mre11-Rad50-Nbs1 (MRN) assemble with T antigen and other viral DNA replication proteins in large nuclear foci. During infection, steady-state levels of MRN subunits decline, although the corresponding mRNA levels remain unchanged. A proteasome inhibitor stabilizes the MRN complex, suggesting that MRN may undergo proteasome-dependent degradation. Analysis of mutant T antigens with disrupted binding to the ubiquitin ligase CUL7 revealed that MRN subunits are stable in cells infected with mutant virus or transfected with mutant viral DNA, implicating CUL7 association with T antigen in MRN proteolysis. The mutant genomes produce fewer virus progeny than the wild type, suggesting that T antigen-CUL7-directed proteolysis facilitates virus propagation. Use of a specific ATM kinase inhibitor showed that ATM kinase signaling is a prerequisite for proteasome-dependent degradation of MRN subunits as well as for the localization of T antigen and damage-signaling proteins to viral replication foci and optimal viral DNA replication. Taken together, the results indicate that SV40 infection manipulates host DNA damage-signaling to reprogram the cell for viral replication, perhaps through mechanisms related to host recovery from DNA damage.
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Kim, Taeg S., Matthew M. Hufford, Jie Sun, Yang-Xin Fu, and Thomas J. Braciale. "Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells after acute virus infection." Journal of Experimental Medicine 207, no. 6 (May 31, 2010): 1161–72. http://dx.doi.org/10.1084/jem.20092017.
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Acute viral infections induce robust adaptive immune responses resulting in virus clearance. Recent evidence suggests that there may be depots of viral antigen that persist in draining lymph nodes (DLNs) after virus clearance and could, therefore, affect the adaptive immune response and memory T cell formation. The nature of these residual antigen depots, the mechanism of antigen persistence, and the impact of the persistent antigen on memory T cells remain ill defined. Using a mouse model of influenza virus infection of the respiratory tract, we identified respiratory dendritic cells (RDCs) as essential for both sampling and presenting residual viral antigen. RDCs in the previously infected lung capture residual viral antigen deposited in an irradiation-resistant cell type. RDCs then transport the viral antigen to the LNs draining the site of infection, where they present the antigen to T cells. Lastly, we document preferential localization of memory T cells to the DLNs after virus clearance as a consequence of presentation of residual viral antigen by the migrant RDC.
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Kennedy, P. G., O. Narayan, Z. Ghotbi, J. Hopkins, H. E. Gendelman, and J. E. Clements. "Persistent expression of Ia antigen and viral genome in visna-maedi virus-induced inflammatory cells. Possible role of lentivirus-induced interferon." Journal of Experimental Medicine 162, no. 6 (December 1, 1985): 1970–82. http://dx.doi.org/10.1084/jem.162.6.1970.
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In this study we investigated the pathogenesis of the lymphoproliferative response in the chronic-active visna maedi virus-induced inflammatory lesions. Viral RNA expression was confined to macrophages, but only in tissues showing inflammatory lesions. A persistent and high level of Ia antigen expression was seen in macrophage-like cells in the inflammatory lesions, and the amounts of viral RNA and Ia expression were closely correlated. A small subpopulation of macrophages contained both viral RNA and Ia antigen, and these were found in greatest number in the lung. In vitro experiments showed that a lentivirus-induced interferon (LV-IFN) could induce Ia antigens in normal sheep spleen and lymph node cells as well as in a transformed sheep macrophage cell line. Ia antigen expression in macrophages was transient in the absence of a continuing IFN stimulus and persisted for at least 2 wk in the presence of LV-IFN. LV-IFN also restricted viral replication in macrophages. It is suggested that LV-IFN induced by the inflammatory cells in visna-maedi lesions may induce Ia antigen expression in macrophages, thereby indirectly causing the lymphoproliferative response and restricted virus replication.
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Rogovskaya, Yuliya, Roman Botalov, and Vyacheslav Ryabov. "Histopathologic, Immunohistochemical Features and Profile of Viral Antigens in Patients with Myocarditis." Advanced Materials Research 1085 (February 2015): 447–52. http://dx.doi.org/10.4028/www.scientific.net/amr.1085.447.
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We studied medical records and endomyocardial biopsies of patients with morphological confirmed lymphocytic myocarditis. The patients were divided into two groups: 1 - patients with arrhythmias; group 2 - patients with predominance syndrome heart failure. Morphological verification of myocarditis was based on World Heart Federation Consensus definition of Inflammatory Cardiomyopathy, 1997. Immunohistological study was performed to identify antigens of cardiotrophic viruses. We revealed some features in topic and character of morphological changes in depending on clinical scenario of myocarditis. In patients with chronic heart failure due to myocarditis revealed a high incidence of expression of LMP-antigen Epstein-Barr virus, the lack of expression of adenovirus antigens. Arrhythmic presentation of myocarditis was characterized by a high frequency of expression of enteroviral VP-1 antigen and the type 1 antigen herpes virus. We were not detected expression of the VP-2 antigen parvovirus B19. As a result the most severe inflammatory changes and interstitial fibrosis of intraventricular septum, widespread damage of myocytes the severe myocardial remodeling was found in patients with presentation of myocarditis by chronic heart failure. Interstitial fibrosis of the outflow tracts of the right ventricle, the low activity of inflammation and mild fibrotic changes were feature of arrhythmic scenario of myocarditis.
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Ogata, Alana F., Adam M. Maley, Connie Wu, Tal Gilboa, Maia Norman, Roey Lazarovits, Chih-Ping Mao, et al. "Ultra-Sensitive Serial Profiling of SARS-CoV-2 Antigens and Antibodies in Plasma to Understand Disease Progression in COVID-19 Patients with Severe Disease." Clinical Chemistry 66, no. 12 (November 30, 2020): 1562–72. http://dx.doi.org/10.1093/clinchem/hvaa213.
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Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 21 million people worldwide since August 16, 2020. Compared to PCR and serology tests, SARS-CoV-2 antigen assays are underdeveloped, despite their potential to identify active infection and monitor disease progression. Methods We used Single Molecule Array (Simoa) assays to quantitatively detect SARS-CoV-2 spike, S1 subunit, and nucleocapsid antigens in the plasma of patients with coronavirus disease (COVID-19). We studied plasma from 64 patients who were COVID-19 positive, 17 who were COVID-19 negative, and 34 prepandemic patients. Combined with Simoa anti-SARS-CoV-2 serological assays, we quantified changes in 31 SARS-CoV-2 biomarkers in 272 longitudinal plasma samples obtained for 39 patients with COVID-19. Data were analyzed by hierarchical clustering and were compared to longitudinal RT-PCR test results and clinical outcomes. Results SARS-CoV-2 S1 and N antigens were detectable in 41 out of 64 COVID-19 positive patients. In these patients, full antigen clearance in plasma was observed a mean ± 95% CI of 5 ± 1 days after seroconversion and nasopharyngeal RT-PCR tests reported positive results for 15 ± 5 days after viral-antigen clearance. Correlation between patients with high concentrations of S1 antigen and ICU admission (77%) and time to intubation (within 1 day) was statistically significant. Conclusions The reported SARS-CoV-2 Simoa antigen assay is the first to detect viral antigens in the plasma of patients who were COVID-19 positive to date. These data show that SARS-CoV-2 viral antigens in the blood are associated with disease progression, such as respiratory failure, in COVID-19 cases with severe disease.
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Gil-Torregrosa, Beatriz C., A. Raúl Castaño, and Margarita Del Val. "Major Histocompatibility Complex Class I Viral Antigen Processing in the Secretory Pathway Defined by the trans-Golgi Network Protease Furin." Journal of Experimental Medicine 188, no. 6 (September 21, 1998): 1105–16. http://dx.doi.org/10.1084/jem.188.6.1105.
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Classical antigen presentation by major histocompatibility complex class I molecules involves cytosolic processing of endogenously synthesized antigens by proteasomes and translocation of processed peptides into the endoplasmic reticulum (ER) by transporters associated with antigen presentation (TAP). Alternative pathways for processing of endogenous antigens, generally involving the ER, have been suggested but not fully proved. We analyzed the potential for class I presentation of proteolytic maturation of secretory antigens in the exocytic pathway. We found that hepatitis B (HB) virus secretory core protein HBe can efficiently deliver COOH-terminally located antigenic peptides for endogenous class I loading in the absence of TAP. Antigen presentation to specific cytotoxic T lymphocytes correlates with protein maturation at the COOH terminus, since modification of maturation and transport of HBe through the secretory pathway alters antigen presentation. Both maturation and a necessary processing step occur in the Golgi or post-Golgi compartment. Antigen presentation is independent of proteasome activity, but inhibitors of the trans-Golgi network resident protease furin inhibit both HBe maturation and antigen presentation. These results define a new antigen processing pathway located in the secretory route, with a central role for proteolytic maturation mediated by the subtilisin protease family member furin as an efficient source for antigen presentation.
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Hawkins, E., and R. Cumming. "Enhanced chemiluminescence for tissue antigen and cellular viral DNA detection." Journal of Histochemistry & Cytochemistry 38, no. 3 (March 1990): 415–19. http://dx.doi.org/10.1177/38.3.1689340.
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The ability to use enhanced chemiluminescence (ECL) to detect horseradish peroxidase as a label for tissue antigens and cellular viral DNA was demonstrated. A liquid nitrogen-cooled charged-coupled device (CCD) was used to detect light output, which was visualized on a monitor or was quantitated using an attached microcomputer. In a tissue antigen model, equivalent sensitivity was observed between ECL and colorimetric detection.
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Kim, Taeg, Matthew Hufford, Jie Sun, and Thomas Braciale. "Antigen persistence and the control of local T cell memory by migrant respiratory dendritic cells following acute virus infection (92.11)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 92.11. http://dx.doi.org/10.4049/jimmunol.184.supp.92.11.
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Abstract Acute viral infections induce robust adaptive immune responses resulting in virus clearance. Recent evidence suggests that there may be depots of viral antigen which persist in draining lymph nodes following virus clearance and could therefore affect the adaptive immune response and memory formation. The nature of these residual antigen depots, the mechanism of antigen persistence and impact of the persistent antigen on memory T cells remains ill-defined. Employing a murine model of influenza virus infection of the respiratory tract, we have identified respiratory dendritic cells (RDC) as an essential cell responsible for both sampling and presenting residual viral antigen. RDC in the previously infected lung capture residual viral antigen deposited in an irradiation resistant cell type(s) and transport the viral antigen to the local lymph nodes draining the site of infection where the migrant RDC present the antigen to T cells. Furthermore, we demonstrate that there is preferential localization of memory T cells to the DLN following virus clearance as a consequence of presentation of residual viral antigen by the migrant RDC to T cells in the DLN. This enriched population of antigen-specific T cells maintained in the antigen draining LN would likely provide a more rapid and robust recall T cell response to a re-infection.
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Gao, Jin, Hongquan Wan, Xing Li, Mira Rakic Martinez, Laura Klenow, Yamei Gao, Zhiping Ye, and Robert Daniels. "Balancing the influenza neuraminidase and hemagglutinin responses by exchanging the vaccine virus backbone." PLOS Pathogens 17, no. 4 (April 19, 2021): e1009171. http://dx.doi.org/10.1371/journal.ppat.1009171.
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Virions are a common antigen source for many viral vaccines. One limitation to using virions is that the antigen abundance is determined by the content of each protein in the virus. This caveat especially applies to viral-based influenza vaccines where the low abundance of the neuraminidase (NA) surface antigen remains a bottleneck for improving the NA antibody response. Our systematic analysis using recent H1N1 vaccine antigens demonstrates that the NA to hemagglutinin (HA) ratio in virions can be improved by exchanging the viral backbone internal genes, especially the segment encoding the polymerase PB1 subunit. The purified inactivated virions with higher NA content show a more spherical morphology, a shift in the balance between the HA receptor binding and NA receptor release functions, and induce a better NA inhibitory antibody response in mice. These results indicate that influenza viruses support a range of ratios for a given NA and HA pair which can be used to produce viral-based influenza vaccines with higher NA content that can elicit more balanced neutralizing antibody responses to NA and HA.
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Han, Wei, Mingxing Gao, Changqing Xie, Jinhua Zhang, Zikai Zhao, Xueying Hu, Wanpo Zhang, et al. "Precise localization and dynamic distribution of Japanese encephalitis virus in the rain nuclei of infected mice." PLOS Neglected Tropical Diseases 15, no. 6 (June 21, 2021): e0008442. http://dx.doi.org/10.1371/journal.pntd.0008442.
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Japanese encephalitis virus (JEV) is a pathogen that causes severe vector-borne zoonotic diseases, thereby posing a serious threat to human health. Although JEV is potentially neurotropic, its pathogenesis and distribution in the host have not been fully elucidated. In this study, an infected mouse model was established using a highly virulent P3 strain of JEV. Immunohistochemistry and in situ hybridization, combined with anatomical imaging of the mouse brain, were used to dynamically localize the virus and construct three-dimensional (3D) images. Consequently, onset of mild clinical signs occurred in some mice at 3.5 d post JEV infection, while most mice displayed typical neurological signs at 6 d post-infection (dpi). Moreover, brain pathology revealed typical changes associated with non-suppurative encephalitis, which lasted up to 8 d. The earliest detection of viral antigen was achieved at 3 dpi in the thalamus and medulla oblongata. At 6 dpi, the positive viral antigen signals were mainly distributed in the cerebral cortex, olfactory area, basal ganglia, thalamus, and brainstem regions in mice. At 8 dpi, the antigen signals gradually decreased, and the localization of JEV tended to concentrate in the cerebrum and thalamus, while no viral antigen was detected in the brain at 21 dpi. In this model, the viral antigen was first expressed in the reticular thalamic nucleus (Rt), and the virus content is relatively stable. The expression of the viral antigen in the hippocampal CA2 region, the anterior olfactory nucleus, and the deep mesencephalic nucleus was high and persistent. The 3D images showed that viral signals were mostly concentrated in the parietal cortex, occipital lobe, and hippocampus, near the mid-sagittal plane. In the early stages of infection in mice, a large number of viral antigens were detected in denatured and necrotic neurons, suggesting that JEV directly causes neuronal damage. From the time of its entry, JEV is widely distributed in the central nervous system thereby causing extensive damage.
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Chen, Dexiang, Kathleen F. Weis, Qili Chu, Cherie Erickson, Ryan Endres, Chris R. Lively, Jorge Osorio, and Lendon G. Payne. "Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses." Journal of Virology 75, no. 23 (December 1, 2001): 11630–40. http://dx.doi.org/10.1128/jvi.75.23.11630-11640.2001.
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ABSTRACT Cytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5- to 2.5-μm gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice. EPI with hepatitis B surface antigen (HBsAg) and a synthetic peptide of influenza virus nucleoprotein (NP peptide) elicited antigen-specific CTL responses as well as antibody responses. In an in vitro cell depletion experiment, we demonstrated that the CTL activity against HBsAg elicited by EPI was attributed to CD8+, not CD4+, T cells. As controls, needle injections of HBsAg or the NP peptide into deeper tissues elicited solely antibody, not CTL, responses. We further demonstrated that EPI with inactivated A/Aichi/68 (H3N2) or A/Sydney/97 (H3N2) influenza virus elicited complete protection against a mouse-adapted A/Aichi/68 virus. In summary, EPI directly delivers protein antigens to the cytosol of the LCs in the skin and elicits both cellular and antibody responses.
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Weisshart, Klaus, Poonam Taneja, Andreas Jenne, Utz Herbig, Daniel T. Simmons, and Ellen Fanning. "Two Regions of Simian Virus 40 T Antigen Determine Cooperativity of Double-Hexamer Assembly on the Viral Origin of DNA Replication and Promote Hexamer Interactions during Bidirectional Origin DNA Unwinding." Journal of Virology 73, no. 3 (March 1, 1999): 2201–11. http://dx.doi.org/10.1128/jvi.73.3.2201-2211.1999.
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ABSTRACT Phosphorylation of simian virus 40 large tumor (T) antigen on threonine 124 is essential for viral DNA replication. A mutant T antigen (T124A), in which this threonine was replaced by alanine, has helicase activity, assembles double hexamers on viral-origin DNA, and locally distorts the origin DNA structure, but it cannot catalyze origin DNA unwinding. A class of T-antigen mutants with single-amino-acid substitutions in the DNA binding domain (class 4) has remarkably similar properties, although these proteins are phosphorylated on threonine 124, as we show here. By comparing the DNA binding properties of the T124A and class 4 mutant proteins with those of the wild type, we demonstrate that mutant double hexamers bind to viral origin DNA with reduced cooperativity. We report that T124A T-antigen subunits impair the ability of double hexamers containing the wild-type protein to unwind viral origin DNA, suggesting that interactions between hexamers are also required for unwinding. Moreover, the T124A and class 4 mutant T antigens display dominant-negative inhibition of the viral DNA replication activity of the wild-type protein. We propose that interactions between hexamers, mediated through the DNA binding domain and the N-terminal phosphorylated region of T antigen, play a role in double-hexamer assembly and origin DNA unwinding. We speculate that one surface of the DNA binding domain in each subunit of one hexamer may form a docking site that can interact with each subunit in the other hexamer, either directly with the N-terminal phosphorylated region or with another region that is regulated by phosphorylation.
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Khan, Tahsin N., Jana L. Mooster, Augustus M. Kilgore, Jossef F. Osborn, and Jeffrey C. Nolz. "Local antigen in nonlymphoid tissue promotes resident memory CD8+ T cell formation during viral infection." Journal of Experimental Medicine 213, no. 6 (May 23, 2016): 951–66. http://dx.doi.org/10.1084/jem.20151855.
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Tissue-resident memory (Trm) CD8+ T cells are functionally distinct from their circulating counterparts and are potent mediators of host protection against reinfection. Whether local recognition of antigen in nonlymphoid tissues during infection can impact the formation of Trm populations remains unresolved. Using skin infections with vaccinia virus (VacV)–expressing model antigens, we found that local antigen recognition had a profound impact on Trm formation. Activated CD8+ T cells trafficked to VacV-infected skin in an inflammation-dependent, but antigen-independent, manner. However, after viral clearance, there was a subsequent ∼50-fold increase in Trm formation when antigen was present in the tissue microenvironment. Secondary antigen stimulation in nonlymphoid tissue caused CD8+ T cells to rapidly express CD69 and be retained at the site of infection. Finally, Trm CD8+ T cells that formed during VacV infection in an antigen-dependent manner became potent stimulators of localized antigen-specific inflammatory responses in the skin. Thus, our studies indicate that the presence of antigen in the nonlymphoid tissue microenvironment plays a critical role in the formation of functional Trm CD8+ T cell populations, a finding with relevance for both vaccine design and prevention of inflammatory disorders.
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Melhem, Nada M., Sherrianne M. Gleason, Xiang Dong Liu, and Simon M. Barratt-Boyes. "High-Level Antigen Expression and Sustained Antigen Presentation in Dendritic Cells Nucleofected with Wild-Type Viral mRNA but Not DNA." Clinical and Vaccine Immunology 15, no. 9 (July 30, 2008): 1337–44. http://dx.doi.org/10.1128/cvi.00154-08.
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ABSTRACT Dendritic cells (DC) are potent antigen-presenting cells that hold promise as cell-based therapeutic vaccines for infectious diseases and cancer. Ideally, DC would be engineered to express autologous viral or tumor antigens to ensure the presentation of relevant antigens to host T cells in vivo; however, expression of wild-type viral genes in primary cell lines can be problematic. Nucleofection is an effective means of delivering transgenes to primary cell lines, but its use in transfecting DNA or mRNA into DC has not been widely investigated. We show that nucleofection is a superior means of transfecting human and monkey monocyte-derived DC with DNA and mRNA compared to lipofection and conventional electroporation. However, the delivery of DNA and mRNA had significantly different outcomes in transfected DC. DC nucleofected with DNA encoding green fluorescent protein (GFP) had poor antigen expression and viability and were refractory to maturation with CD40 ligand. In contrast, >90% of DC expressed uniform and high levels of GFP from 3 h to 96 h postnucleofection with mRNA while maintaining a normal maturation response to CD40 ligation. Monkey DC nucleofected with wild-type, non-codon-optimized mRNA encoding simian immunodeficiency virus Gag stimulated robust antigen-specific effector T-cell responses at 24 h and 48 h postnucleofection, reflecting sustained antigen presentation in transfected DC, whereas no detectable T-cell response was noted when DC were nucleofected with DNA encoding the same Gag sequence. These data indicate that mRNA nucleofection may be an optimal means of transfecting DC with autologous tumor or viral antigen for DC-based immunotherapy.
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Netski, Dale, Brandolyn H. Thran, and Stephen C. St. Jeor. "Sin Nombre Virus Pathogenesis inPeromyscus maniculatus." Journal of Virology 73, no. 1 (January 1, 1999): 585–91. http://dx.doi.org/10.1128/jvi.73.1.585-591.1999.
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ABSTRACT Sin Nombre virus (SNV), a member of the Hantavirusgenus, causes acute viral pneumonia in humans and is thought to persistently infect mice. The deer mouse, Peromyscus maniculatus, has been identified as the primary reservoir host for SNV. To understand SNV infection of P. maniculatus, we examined wild deer mice for localization of viral antigens and nucleic acid. Morphologic examination consistently revealed septal edema within lung tissue and mononuclear cell infiltrates in portal areas of the liver. Immunohistochemical analysis of SNV-infected deer mice identified viral antigens within lung, liver, kidney, and spleen. The lungs consistently presented with the highest levels of viral antigen by immunohistochemistry and with the highest levels of nucleic acid by reverse transcriptase (RT) PCR. The mononuclear cell infiltrates surrounding liver portal triads were positive for SNV antigens in addition to resident macrophages in liver sinuses. Spleen tissue contained antigens in both the red pulp and the periartereolar region of the white pulp. The kidney presented with no gross pathology, although antigens could be localized to glomeruli. Virus antigen levels within the kidney were highest in deer mice that did not have antibodies to SNV but contained viral nucleic acid detectable by RT PCR. Since transmission is thought to occur via urine, our results suggest that virus transmission may be highest in the early stages of infection. In addition, these results indicate that SNV does cause some pathology within its reservoir host.
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Hadziyannis, Emilia, and Andreas Laras. "Viral Biomarkers in Chronic HBeAg Negative HBV Infection." Genes 9, no. 10 (September 27, 2018): 469. http://dx.doi.org/10.3390/genes9100469.
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Viral biomarkers are important tools for monitoring chronic hepatitis B virus (HBV) hepatitis B early antigen (HBeAg) negative infection, both in its natural course as well as during and after treatment. The biomarkers consist of antibodies against viral epitopes, viral proteins, and molecular surrogate markers of the quantity and transcriptional activity of the stable episomal HBV covalently closed circular DNA (cccDNA) which is located in the nuclei of the infected hepatocytes. HBV deoxyribonucleic acid (DNA) or else viral load measurement in plasma or serum is a marker of HBV replication of major clinical importance. HBV DNA is used for staging and treatment monitoring as described in international scientific guidelines. Quantification of HBV antigens, mainly hepatitis B surface antigen (HBsAg) as well as Hepatitis B core related antigen (HBcrAg), play an important yet secondary role, especially in cases of low or undetectable HBV DNA and has been evaluated for the classification of the inactive carrier state, as a predictor of subsequent HBsAg clearance, treatment outcome, and development of hepatocellular carcinoma (HCC). The measurement of the replicative intermediate HBV RNA in serum is currently evaluated and may also prove to be a significant biomarker particularly in patients treated with nucleot(s)ide analogs. This review focuses on the viral biomarkers mentioned above and their role in HBV, HBeAg negative, infection.
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Alatortseva, G. I., A. V. Sidorov, L. N. Nesterenko, L. N. Luhverchik, I. I. Amiantova, V. V. Docenko, Phong Pham Huy, et al. "Recombinant Analogue of Varicella Zoster Virus Glycoprotein E: Cloning, Expression and Studying of AntigEn Properties." Epidemiology and Vaccine Prevention 15, no. 1 (February 20, 2016): 77–85. http://dx.doi.org/10.31631/2073-3046-2016-15-1-77-85.
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We made recombinant antigen GE containing fragment of VZV glycoprotein E (Gly48 - Glu135) fused to E. coli beta-galactosidase and confirmed its antigen specificity by Western blotting and competitive-inhibition enzyme immunoassay (EIA) in comparison with commercial analogues and natural viral antigens. We showed interaction of recombinant GE protein with IgG antibodies from rabbits immunized by vaccine viral strain. GE protein also specifically reacted in ELISA with 66% of sera from zoster patients and 35% of sera from control groups including sera containing antibodies to other herpes viruses, sera from healthy donors, and sera from patients with different forms of intestinal disorders. Consequently, we demonstrated possibility of application of our recombinant GE VZV as antigen for diagnostics and research use.
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Weller, Melodie L., Matthew R. Gardener, Zoe C. Bogus, Michael A. Smith, Elisa Astorri, Drew G. Michael, Donald A. Michael, et al. "Hepatitis Delta Virus Detected in Salivary Glands of Sjögren’s Syndrome Patients and Recapitulates a Sjögren’s Syndrome-Like Phenotype in Vivo." Pathogens and Immunity 1, no. 1 (May 23, 2016): 12. http://dx.doi.org/10.20411/pai.v1i1.72.
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Background: Low-level, chronic viral infections have been suspect in the development of select autoimmune diseases, including primary Sjögren’s syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues suggestive of a viral infection. Yet, with this data in hand, a causal link between a viral infection and development of pSS had not been identified. Therefore, a study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease.Methods: A viral microarray was utilized to measure viral transcripts present in salivary gland tissue from patients diagnosed with pSS compared to healthy controls. Murine models of salivary gland localized HDV antigen expression were developed to evaluate the capacity of a chronic HDV signature to trigger the development of a pSS-like phenotype.Results: Through this analysis, two distinct viral profiles were identified, including the increased presence of hepatitis delta virus (HDV) in 50% of pSS patients evaluated. Presence of HDV antigen and sequence were confirmed in minor salivary gland tissue. Patients with elevated HDV levels in salivary gland tissue were negative for detectible hepatitis B virus (HBV) surface antigen and antibodies to HBV or HDV. Expression of HDV antigens in vivo resulted in reduced stimulated saliva flow, increase in focal lymphocytic infiltrates, and development of autoantibodies.Conclusion: Identification of HDV in pSS patients and induction of a complete pSS-like phenotype in vivo provides further support of a viral-mediated etiopathology in the development of pSS.
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Graham, Barney S., Morgan S. A. Gilman, and Jason S. McLellan. "Structure-Based Vaccine Antigen Design." Annual Review of Medicine 70, no. 1 (January 27, 2019): 91–104. http://dx.doi.org/10.1146/annurev-med-121217-094234.
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Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens, particularly difficult targets that have resisted prior vaccine development efforts. Solving viral surface protein structures also supports rapid vaccine antigen design and application of platform manufacturing approaches for emerging pathogens.
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Nikzad, Rana, Laura S. Angelo, Kevin Aviles-Padilla, Duy T. Le, Vipul K. Singh, Lynn Bimler, Milica Vukmanovic-Stejic, et al. "Human natural killer cells mediate adaptive immunity to viral antigens." Science Immunology 4, no. 35 (May 10, 2019): eaat8116. http://dx.doi.org/10.1126/sciimmunol.aat8116.
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Adaptive immune responses are defined as antigen sensitization–dependent and antigen-specific responses leading to establishment of long-lived immunological memory. Although natural killer (NK) cells have traditionally been considered cells of the innate immune system, mounting evidence in mice and nonhuman primates warrants reconsideration of the existing paradigm that B and T cells are the sole mediators of adaptive immunity. However, it is currently unknown whether human NK cells can exhibit adaptive immune responses. We therefore tested whether human NK cells mediate adaptive immunity to virally encoded antigens using humanized mice and human volunteers. We found that human NK cells displayed vaccination-dependent, antigen-specific recall responses in vitro, when isolated from livers of humanized mice previously vaccinated with HIV-encoded envelope protein. Furthermore, we discovered that large numbers of cytotoxic NK cells with a tissue-resident phenotype were recruited to sites of varicella-zoster virus (VZV) skin test antigen challenge in VZV-experienced human volunteers. These NK-mediated recall responses in humans occurred decades after initial VZV exposure, demonstrating that NK memory in humans is long-lived. Our data demonstrate that human NK cells exhibit adaptive immune responses upon vaccination or infection. The existence of human memory NK cells may allow for the development of vaccination-based approaches capable of establishing potent NK-mediated memory functions contributing to host protection.
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Tamburini, Beth, Matthew Burchill, and Ross Kedl. "Antigen archiving and management by lymphatic endothelial cells. (INC1P.363)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 54.20. http://dx.doi.org/10.4049/jimmunol.194.supp.54.20.
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Abstract Antigen derived from virus infections such as influenza and Vesicular Stomatitis Virus (VSV) can persist well beyond the natural rise and fall of the adaptive immune response against the infection. Antigen can similarly persist following both viral Vaccinia challenge and subunit vaccination. Surprisingly, persisting antigen from either Vaccinia or subunit vaccination is captured and maintained by a stromal cell subset: Lymphatic Endothelial Cells (LECs). The duration of antigen persistence is directly correlated with antigen dose and pattern recognition receptor (PRR) activation. PRR induced inflammation leads to LEC proliferation followed by antigen persistence in the lymph node. The coupling of LEC proliferation and antigen capture identifies a novel mechanism by which the secondary lymphoid stroma stores, or “archives”, antigens for extended periods of time after antigen challenge. Consistent with the idea that viral antigen persistence impacts the function of circulating memory T cells, we find that vaccine elicited antigen archiving on LECs has a significant impact on the fate of circulating memory T cells. As such, antigen archiving on LECs leads to increased production of interferon gamma and interleukin 2 by antigen specific CD8 T cells and protection against secondary infection. These findings may broadly impact our understanding of how lymph node stroma, specifically LECs, are involved in i) managing antigen and ii) protecting against re-infection.
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Milosevic, Slavoljub, Uta Behrends, Dinesh Adhikary, and Josef Mautner. "Identification of Major Histocompatibility Complex Class II-Restricted Antigens and Epitopes of the Epstein-Barr Virus by a Novel Bacterial Expression Cloning Approach." Journal of Virology 80, no. 21 (November 1, 2006): 10357–64. http://dx.doi.org/10.1128/jvi.01193-06.
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ABSTRACT Epstein-Barr virus (EBV)-specific T cells have been successfully used to treat or prevent EBV-positive lymphoproliferative disease in hematopoietic stem cell transplant recipients, but the antigens recognized by the infused CD4+ T cells have remained unknown. Here, we describe a simple procedure that permits the identification of viral T-helper (TH)-cell antigens and epitopes. This direct antigen identification method is based on the random expression of viral polypeptides fused to chloramphenicol acetyltransferase (CAT) in bacteria, which are subsequently fed to major histocompatibility complex class II+ antigen-presenting cells and probed with antigen-specific T cells. The fusion of antigenic fragments to CAT offers several advantages. First, chloramphenicol treatment allows the selection of bacteria expressing antigen-CAT fusion proteins in frame, which greatly reduces the number of colonies to be screened. Second, antigenic fragments fused to CAT are expressed at high levels, even when derived from proteins that are toxic to bacteria. Third, the uniformly high expression level of antigen-CAT fusion proteins permits the establishment of large and representative pool sizes. Finally, antigen identification does not require knowledge of the restriction element and often leads directly to the identification of the T-cell epitope. Using this approach, the BALF4 and BNRF1 proteins were identified as targets of the EBV-specific T-helper-cell response, demonstrating that lytic cycle antigens are a relevant component of the EBV-specific TH-cell response.
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Xue, Ning, Shan Xing, Weiguo Ma, Jiahe Sheng, Zhiliang Huang, and Qingxia Xu. "Combination of Plasma MIF and VCA-IgA Improves the Diagnostic Specificity for Patients With Nasopharyngeal Carcinoma." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382093577. http://dx.doi.org/10.1177/1533033820935773.
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Introduction: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma. Materials and Methods: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques. Results: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen–negative and Epstein-Barr virus viral capsid antigen–positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen. Conclusion: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.