Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo

A common strategy shared by all known gammaherpesviruses is their ability to establish a latent infection in lymphocytes--predominantly in B cells. In immunocompromised patients, such as transplant recipients or AIDS patients, gammaherpesvirus infections can lead to the development of lymphoprolifer...

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Bibliographic Details
Published in:PloS one 2014-08, Vol.9 (8), p.e105197-e105197
Main Authors: Rangaswamy, Udaya S, O'Flaherty, Brigid M, Speck, Samuel H
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Activation
AIDS
Analysis
Animals
B cells
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B-Lymphocytes - virology
Biology and Life Sciences
Cell cycle
Cell differentiation
Cell Differentiation - immunology
Cytokines
Cytomegalovirus
Dendritic cells
Development and progression
Differentiation (biology)
Gammaherpesvirinae - physiology
Genomes
Health aspects
Herpesviridae Infections - immunology
Herpesviridae Infections - virology
Immune response
Immunocompromised hosts
Immunology
In vivo methods and tests
Infection
Infections
Inoculation
Interleukin 10
Interleukin-10 - biosynthesis
Latency
Latent infection
Lymphocyte Activation - immunology
Lymphocytes
Lymphocytes B
Lymphoma
Machinery and equipment
Medicine
Mice
Mutants
Mutation
Pathogenesis
Patients
Phenols (Class of compounds)
Phosphorylation
Plasma Cells - immunology
Plasma Cells - metabolism
Plasma Cells - virology
Proteins
Signal Transduction
Signaling
STAT5 Transcription Factor - metabolism
Tyrosine
Tyrosine - chemistry
Viral Proteins - chemistry
Viral Proteins - genetics
Viral Proteins - metabolism
Virus Activation
Virus Latency
Viruses
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Summary:A common strategy shared by all known gammaherpesviruses is their ability to establish a latent infection in lymphocytes--predominantly in B cells. In immunocompromised patients, such as transplant recipients or AIDS patients, gammaherpesvirus infections can lead to the development of lymphoproliferative disease and lymphoid malignancies. The human gamma-herpesviruses, EBV and KSHV, encode proteins that are capable of modulating the host immune signaling machinery, thereby subverting host immune responses. Murine gamma-herpesvirus 68 (MHV68) infection of laboratory strains of mice has proven to be useful small-animal model that shares important pathogenic strategies with the human gamma-herpesviruses. The MHV68 M2 protein is known to manipulate B cell signaling and, dependent on route and dose of virus inoculation, plays a role in both the establishment of latency and virus reactivation. M2 contains two tyrosines that are targets for phosphorylation, and have been shown to interact with the B cell signaling machinery. Here we describe in vitro and in vivo studies of M2 mutants which reveals that while both tyrosines Y120 and Y129 are required for M2 induction of IL-10 expression from primary murine B cells in vitro, only Y129 is critical for reactivation from latency and plasma cell differentiation in vivo.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0105197