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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Main Authors: Udaya S Rangaswamy, Brigid M O'Flaherty, Samuel H Speck
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4133380?pdf=render
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author Udaya S Rangaswamy
Brigid M O'Flaherty
Samuel H Speck
author_facet Udaya S Rangaswamy
Brigid M O'Flaherty
Samuel H Speck
author_sort Udaya S Rangaswamy
collection DOAJ
description 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.
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spelling doaj.art-436c6d81256b45828faa02651de37a812022-12-22T01:13:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0198e10519710.1371/journal.pone.0105197Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.Udaya S RangaswamyBrigid M O'FlahertySamuel H SpeckA 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.http://europepmc.org/articles/PMC4133380?pdf=render
spellingShingle Udaya S Rangaswamy
Brigid M O'Flaherty
Samuel H Speck
Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
PLoS ONE
title Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
title_full Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
title_fullStr Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
title_full_unstemmed Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
title_short Tyrosine 129 of the murine gammaherpesvirus M2 protein is critical for M2 function in vivo.
title_sort tyrosine 129 of the murine gammaherpesvirus m2 protein is critical for m2 function in vivo
url http://europepmc.org/articles/PMC4133380?pdf=render
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