414 results match your criteria gammaherpesvirus latency

The ENE of polyadenylated nuclear (PAN) RNA is not required for productive lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV).

J Virol 2021 Apr 14. Epub 2021 Apr 14.

Department of Microbiology & Immunology, University of Nevada, Reno School of Medicine, Reno, Nevada, USA

KSHV is an oncogenic human gammaherpesvirus and the causative agent of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multi-centric Castleman's disease (MCD). During reactivation, viral genes are expressed in a temporal manner. These lytic genes encode for transactivators, core replication proteins, or structural proteins. Read More

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The role of EBV in hematolymphoid proliferations: Emerging concepts relevant to diagnosis and treatment.

Histopathology 2021 Apr 7. Epub 2021 Apr 7.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus with >90% of the adult population worldwide harboring latent infection. A small subset of those infected develop EBV-associated neoplasms including a range of lymphoproliferative disorders (LPD). The diagnostic distinction of these entities appears increasingly relevant as our understanding of EBV-host interactions and mechanisms of EBV-driven lymphomagenesis improves. Read More

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Gammaherpesvirus Usurps Host IL-17 Signaling To Support the Establishment of Chronic Infection.

mBio 2021 04 6;12(2). Epub 2021 Apr 6.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Gammaherpesviruses establish lifelong infection and are associated with a variety of cancers, including B cell lymphomas. These viruses manipulate the B cell differentiation process to establish lifelong infection in memory B cells. Specifically, gammaherpesviruses infect naive B cells and promote entry of both infected and uninfected naive B cells into germinal centers, where the virus usurps rapid proliferation of germinal center B cells to exponentially increase its cellular latent reservoir. Read More

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Optimized Detection of Acute MHV68 Infection With a Reporter System Identifies Large Peritoneal Macrophages as a Dominant Target of Primary Infection.

Front Microbiol 2021 9;12:656979. Epub 2021 Mar 9.

Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.

Investigating the dynamics of virus-host interactions remains an important challenge, often limited by the ability to directly identify virally infected cells. Here, we utilize a beta-lactamase activated fluorescent substrate to identify primary targets of murine gammaherpesvirus 68 (MHV68) infection in the peritoneal cavity. By optimizing substrate and detection conditions, we were able to achieve multiparameter characterization of infected cells and the ensuing host response. Read More

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Targeting the Kaposi's sarcoma-associated herpesvirus genome with the CRISPR-Cas9 platform in latently infected cells.

Virol J 2021 Mar 17;18(1):56. Epub 2021 Mar 17.

The Concern Foundation at the Lautenberg Center for Immunology and Cancer Research, IMRIC, Hebrew University Faculty of Medicine, 91120, Jerusalem, Israel.

Background: Kaposi's sarcoma-associated herpesvirus (KSHV) is a transforming gammaherpesvirus. Like other herpesviruses, KSHV infection is for life long and there is no treatment that can cure patients from the virus. In addition, there is an urgent need to target viral genes to study their role during the infection cycle. Read More

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Direct Evidence of Abortive Lytic Infection-Mediated Establishment of Epstein-Barr Virus Latency During B-Cell Infection.

Front Microbiol 2020 21;11:575255. Epub 2021 Jan 21.

Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Viral infection induces dynamic changes in transcriptional profiles. Virus-induced and antiviral responses are intertwined during the infection. Epstein-Barr virus (EBV) is a human gammaherpesvirus that provides a model of herpesvirus latency. Read More

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January 2021

Interferon Regulatory Factor 3 Supports the Establishment of Chronic Gammaherpesvirus Infection in a Route- and Dose-Dependent Manner.

J Virol 2021 04 12;95(9). Epub 2021 Apr 12.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are associated with several malignancies, including B cell lymphomas. Uniquely, these viruses manipulate B cell differentiation to establish long-term latency in memory B cells. This study focuses on the interaction between gammaherpesviruses and interferon regulatory factor 3 (IRF-3), a ubiquitously expressed transcription factor with multiple direct target genes, including beta interferon (IFN-β), a type I IFN. Read More

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'Off-the-shelf' allogeneic antigen-specific adoptive T-cell therapy for the treatment of multiple EBV-associated malignancies.

J Immunother Cancer 2021 Feb;9(2)

Immunology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

Background: Epstein-Barr virus (EBV), an oncogenic human gammaherpesvirus, is associated with a wide range of human malignancies of epithelial and B-cell origin. Recent studies have demonstrated promising safety and clinical efficacy of allogeneic 'off-the-shelf' virus-specific T-cell therapies for post-transplant viral complications.

Methods: Taking a clue from these studies, we developed a highly efficient EBV-specific T-cell expansion process using a replication-deficient AdE1-LMPpoly vector that specifically targets EBV-encoded nuclear antigen 1 (EBNA1) and latent membrane proteins 1 and 2 (LMP1 and LMP2), expressed in latency II malignancies. Read More

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February 2021

Th2 Cytokine Modulates Herpesvirus Reactivation in a Cell Type Specific Manner.

J Virol 2021 Feb 3. Epub 2021 Feb 3.

Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Gammaherpesviruses, such as Epstein-Barr virus (EBV), Kaposi's sarcoma associated virus (KSHV), and murine γ-herpesvirus 68 (MHV68), establish latent infection in B cells, macrophages, and non-lymphoid cells, and can induce both lymphoid and non-lymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type specific regulation of virus infection. Read More

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February 2021

Multiple Sclerosis-Like Symptoms in Mice Are Driven by Latent γHerpesvirus-68 Infected B Cells.

Front Immunol 2020 19;11:584297. Epub 2020 Nov 19.

Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC, Canada.

Multiple sclerosis (MS) is caused by a combination of genetic and environmental factors. It is believed that previous infection with Epstein Barr Virus (EBV) plays an important role in the development of MS. Previously, we developed a murine model where latent infection with gamma herpesvirus 68 (γHV-68), a murine homolog to EBV, enhanced the symptoms of experimental autoimmune encephalomyelitis (EAE), resulting in disease that more closely resembles MS in humans. Read More

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November 2020

Deletion of immune evasion genes provides an effective vaccine design for tumor-associated herpesviruses.

NPJ Vaccines 2020 Nov 5;5(1):102. Epub 2020 Nov 5.

Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.

Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. However, they also usually sacrifice immunogenicity for attenuation. It is particularly difficult to elicit an effective vaccine for herpesviruses due to an armament of immune evasion genes and a latent phase. Read More

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November 2020

Brd/BET Proteins Influence the Genome-Wide Localization of the Kaposi's Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus Major Latency Proteins.

Front Microbiol 2020 22;11:591778. Epub 2020 Oct 22.

Institut für Virologie, Medizinische Hochschule Hannover, Hanover, Germany.

The Kaposi's Sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus (MHV-68) persist in infected hosts in a latent state that is characterized by the absence of virus production and by restricted viral gene expression. Their major latency protein, the latency-associated nuclear antigen (kLANA for KSHV and mLANA for MHV-68), is essential for viral genome maintenance and replication and involved in transcriptional regulation. Both kLANA and mLANA interact with cellular chromatin-associated proteins, among them the Bromodomain and Extra Terminal domain (Brd/BET) proteins, which recruit cellular and viral proteins to acetylated histones through their bromodomains and modulate cellular gene expression. Read More

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October 2020

Histone Loaders CAF1 and HIRA Restrict Epstein-Barr Virus B-Cell Lytic Reactivation.

mBio 2020 10 27;11(5). Epub 2020 Oct 27.

Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

Epstein-Barr virus (EBV) infects 95% of adults worldwide and causes infectious mononucleosis. EBV is associated with endemic Burkitt lymphoma, Hodgkin lymphoma, posttransplant lymphomas, nasopharyngeal and gastric carcinomas. In these cancers and in most infected B-cells, EBV maintains a state of latency, where nearly 80 lytic cycle antigens are epigenetically suppressed. Read More

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October 2020

Deletion of Murine Gammaherpesvirus Gene in Activation-Induced Cytidine Deaminase-Expressing B Cells Impairs Host Colonization and Viral Reactivation.

J Virol 2020 12 9;95(1). Epub 2020 Dec 9.

Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

Gammaherpesviruses (GHVs) are DNA tumor viruses that establish lifelong, chronic infections in lymphocytes of humans and other mammals. GHV infections are associated with numerous cancers, especially in immunocompromised hosts. While it is known that GHVs utilize host germinal center (GC) B cell responses during latency establishment, an understanding of how viral gene products function in specific B cell subsets to regulate this process is incomplete. Read More

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December 2020

Interferon Regulatory Factor 7 Attenuates Chronic Gammaherpesvirus Infection.

J Virol 2020 11 23;94(24). Epub 2020 Nov 23.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections and are associated with a variety of malignancies, including lymphomas. Interferon regulatory factor 7 (IRF-7) is an innate immune transcription factor that restricts acute replication of diverse viruses, including murine gammaherpesvirus 68 (MHV68). Importantly, very little is known about the role of IRF-7 during chronic virus infections. Read More

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November 2020

Effects of (MusGHV-1) Reactivation in European Badger () Genital Tracts on Reproductive Fitness.

Pathogens 2020 Sep 20;9(9). Epub 2020 Sep 20.

Wildlife Conservation Research Unit, Department of Zoology, University of Oxford, Recanati-Kaplan Centre, Abingdon Road, Tubney House, Tubney, Oxfordshire OX13 5QL, UK.

Reactivation of latent Gammaherpesvirus in the genital tract can lead to reproductive failure in domestic animals. Nevertheless, this pathophysiology has not received formal study in wild mammals. High prevalence of (MusGHV-1) DNA detected in the genital tracts of European badgers () implies that this common pathogen may be a sexual transmitted infection. Read More

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September 2020

KSHV LANA acetylation-selective acidic domain reader sequence mediates virus persistence.

Proc Natl Acad Sci U S A 2020 09 20;117(36):22443-22451. Epub 2020 Aug 20.

Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal;

Viruses modulate biochemical cellular pathways to permit infection. A recently described mechanism mediates selective protein interactions between acidic domain readers and unacetylated, lysine-rich regions, opposite of bromodomain function. Kaposi´s sarcoma (KS)-associated herpesvirus (KSHV) is tightly linked with KS, primary effusion lymphoma, and multicentric Castleman's disease. Read More

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September 2020

Interleukin 16 contributes to gammaherpesvirus pathogenesis by inhibiting viral reactivation.

PLoS Pathog 2020 07 31;16(7):e1008701. Epub 2020 Jul 31.

Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Gammaherpesviruses have evolved various strategies to take advantage of host cellular factors or signaling pathways to establish a lifelong latent infection. Like the human gammaherpesvirus Epstein-Barr virus, murine gammaherpesvirus 68 (MHV68) establishes and maintains latency in the memory B cells during infection of laboratory mice. We have previously shown that MHV68 can immortalize fetal liver-derived B cells that induce lymphomas when injected into immunodeficient mice. Read More

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Dangerous Liaisons: Gammaherpesvirus Subversion of the Immunoglobulin Repertoire.

Viruses 2020 07 23;12(8). Epub 2020 Jul 23.

HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

A common biologic property of the gammaherpesviruses Epstein-Barr Virus and Kaposi sarcoma herpesvirus is their use of B lymphocytes as a reservoir of latency in healthy individuals that can undergo oncogenic transformation later in life. Gammaherpesviruses (GHVs) employ an impressive arsenal of proteins and non-coding RNAs to reprogram lymphocytes for proliferative expansion. Within lymphoid tissues, the germinal center (GC) reaction is a hub of B cell proliferation and death. Read More

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B Cell-Intrinsic Expression of Interferon Regulatory Factor 1 Supports Chronic Murine Gammaherpesvirus 68 Infection.

J Virol 2020 06 16;94(13). Epub 2020 Jun 16.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Gammaherpesviruses are ubiquitous pathogens that are associated with cancers, including B cell lymphomas. These viruses are unique in that they infect naive B cells and subsequently drive a robust polyclonal germinal center response in order to amplify the latent reservoir and to establish lifelong infection in memory B cells. The gammaherpesvirus-driven germinal center response in combination with robust infection of germinal center B cells is thought to precipitate lymphomagenesis. Read More

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ORF6 and ORF61 Expressing MVA Vaccines Impair Early but Not Late Latency in Murine Gammaherpesvirus MHV-68 Infection.

Front Immunol 2019 18;10:2984. Epub 2019 Dec 18.

Institute for Virology, Düsseldorf University Hospital, Heinrich-Heine-University, Düsseldorf, Germany.

Gammaherpesviruses (γHV) are important pathogens causing persistent infections which lead to several malignancies in immunocompromised patients. Murine γHV 68 (MHV-68), a homolog to human EBV and KSHV, has been employed as a classical pathogen to investigate the molecular pathogenicity of γHV infections. γHV express distinct antigens during lytic or latent infection and antigen-specific T cells have a significant role in controlling the acute and latent viral infection, although the quality of anti-viral T cell responses required for protective immunity is not well-understood. Read More

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November 2020

Gammaherpesviruses and B Cells: A Relationship That Lasts a Lifetime.

Viral Immunol 2020 05 8;33(4):316-326. Epub 2020 Jan 8.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

Gammaherpesviruses are highly prevalent pathogens that establish life-long infection and are associated with diverse malignancies, including lymphoproliferative diseases and B cell lymphomas. Unlike other viruses that either do not infect B cells or infect B cells transiently, gammaherpesviruses manipulate physiological B cell differentiation to establish life-long infection in memory B cells. Disruption of such viral manipulation by genetic or environmental causes is likely to seed viral lymphomagenesis. Read More

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The Zebrafish Xenograft Platform-A Novel Tool for Modeling KSHV-Associated Diseases.

Viruses 2019 12 20;12(1). Epub 2019 Dec 20.

Department of Microbiology & Immunology, Dalhousie University, 5850 College Street, Halifax, NS B3H 4R2, Canada.

Kaposi's sarcoma associated-herpesvirus (KSHV, also known as human herpesvirus-8) is a gammaherpesvirus that establishes life-long infection in human B lymphocytes. KSHV infection is typically asymptomatic, but immunosuppression can predispose KSHV-infected individuals to primary effusion lymphoma (PEL); a malignancy driven by aberrant proliferation of latently infected B lymphocytes, and supported by pro-inflammatory cytokines and angiogenic factors produced by cells that succumb to lytic viral replication. Here, we report the development of the first model for a virally induced lymphoma in zebrafish, whereby KSHV-infected PEL tumor cells engraft and proliferate in the yolk sac of zebrafish larvae. Read More

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December 2019

A role of hypoxia-inducible factor 1 alpha in Murine Gammaherpesvirus 68 (MHV68) lytic replication and reactivation from latency.

PLoS Pathog 2019 12 6;15(12):e1008192. Epub 2019 Dec 6.

Department of Microbiology and Immunology and Miami Center for AIDS Research, Miami, Florida, United States of America.

The hypoxia-inducible factor 1 alpha (HIF1α) protein and the hypoxic microenvironment are critical for infection and pathogenesis by the oncogenic gammaherpesviruses (γHV), Kaposi sarcoma herpes virus (KSHV) and Epstein-Barr virus (EBV). However, understanding the role of HIF1α during the virus life cycle and its biological relevance in the context of host has been challenging due to the lack of animal models for human γHV. To study the role of HIF1α, we employed the murine gammaherpesvirus 68 (MHV68), a rodent pathogen that readily infects laboratory mice. Read More

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December 2019

Epstein-Barr virus EBER1 and murine gammaherpesvirus TMER4 share conserved in vivo function to promote B cell egress and dissemination.

Proc Natl Acad Sci U S A 2019 12 3;116(51):25392-25394. Epub 2019 Dec 3.

Department of Molecular Genetics & Microbiology, University of Florida Health Cancer Center, University of Florida, Gainesville, FL 32610

The oncogenic gammaherpesviruses, including human Epstein-Barr virus (EBV), human Kaposi's sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4) establish life-long latency in circulating B cells. The precise determinants that mediate in vivo gammaherpesvirus latency and tumorigenesis remain unclear. The EBV-encoded RNAs (EBERs) are among the first noncoding RNAs ever identified and have been the subject of decades of studies; however, their biological roles during in vivo infection remain unknown. Read More

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December 2019

Low prevalence of human gammaherpesvirus 8 (HHV-8) infection among HIV-infected pregnant women in Rio De Janeiro, Brazil.

J Matern Fetal Neonatal Med 2019 Nov 21:1-4. Epub 2019 Nov 21.

Laboratório de Virologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio De Janeiro, Brazil.

Pregnant women coinfected with the human immunodeficiency virus (HIV) and human gammaherpesvirus 8 (HHV-8) are at higher risk of Kaposi's sarcoma development, increased viral load, and vertical transmission of these viruses. A total of 131 pregnant women infected with HIV were examined for antibodies against HHV-8 latency-associated nuclear antigen (LANA) and lytic antigens using immunofluorescence assays. The presence of HHV-8 DNA was confirmed using real-time polymerase chain reaction (qPCR) and nested PCR. Read More

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November 2019

Identifying the Cellular Interactome of Epstein-Barr Virus Lytic Regulator Zta Reveals Cellular Targets Contributing to Viral Replication.

J Virol 2020 01 17;94(3). Epub 2020 Jan 17.

School of Life Sciences, University of Sussex, Brighton, United Kingdom

The human gammaherpesvirus Epstein-Barr virus (EBV) (human herpesvirus 4 [HHV4]) infects most adults and is an important contributor to the development of many types of lymphoid and epithelial cancers. Essential contributions of viral genes to viral replication are known, but the potential contributions of cell genes are less well delineated. A key player is the viral protein Zta (BZLF1, ZEBRA, or Z). Read More

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January 2020

A comparative epigenome analysis of gammaherpesviruses suggests cis-acting sequence features as critical mediators of rapid polycomb recruitment.

PLoS Pathog 2019 10 31;15(10):e1007838. Epub 2019 Oct 31.

Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.

Latent Kaposi sarcoma-associated herpesvirus (KSHV) genomes rapidly acquire distinct patterns of the activating histone modification H3K4-me3 as well as repressive H3K27-me3 marks, a modification linked to transcriptional silencing by polycomb repressive complexes (PRC). Interestingly, PRCs have recently been reported to restrict viral gene expression in a number of other viral systems, suggesting they may play a broader role in controlling viral chromatin. If so, it is an intriguing possibility that latency establishment may result from viral subversion of polycomb-mediated host responses to exogenous DNA. Read More

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October 2019

Control of Viral Latency by Episome Maintenance Proteins.

Trends Microbiol 2020 02 14;28(2):150-162. Epub 2019 Oct 14.

The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address:

The human DNA tumor viruses Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and human papillomavirus (HPV) share the common property of persisting as multicopy episomes in the nuclei of rapidly dividing host cells. These episomes form the molecular basis for viral latency and are etiologically linked to virus-associated cancers. Episome maintenance requires epigenetic programming to ensure the proper control of viral gene expression, DNA replication, and genome copy number. Read More

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February 2020

B Cell-Intrinsic SHP1 Expression Promotes the Gammaherpesvirus-Driven Germinal Center Response and the Establishment of Chronic Infection.

J Virol 2019 12 12;94(1). Epub 2019 Dec 12.

Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

Gammaherpesviruses are ubiquitous pathogens that establish lifelong infections in the majority of adults worldwide. Chronic gammaherpesvirus infection has been implicated in both lymphomagenesis and, somewhat controversially, autoimmune disease development. Pathogenesis is largely associated with the unique ability of gammaherpesviruses to usurp B cell differentiation, specifically, the germinal center response, to establish long-term latency in memory B cells. Read More

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December 2019