Establishment of murine gammaherpesvirus latency in b cells is not a stochastic event

Jérémie Decalf, Cristina Godinho-Silva, Diana Fontinha, Sofia Marques, J. Pedro Simas

Resultado de pesquisarevisão de pares

14 Citações (Scopus)


Murid γ-herpesvirus-4 (MuHV-4) promotes polyclonal B cell activation and establishes latency in memory B cells via unclear mechanisms. We aimed at exploring whether B cell receptor specificity plays a role in B cell susceptibility to viral latency and how this is related to B cell activation. We first observed that MuHV-4-specific B cells represent a minority of the latent population, and to better understand the influence of the virus on non-MuHV-4 specific B cells we used the SWHEL mouse model, which produce hen egg lysozyme (HEL)-specific B cells. By tracking HEL+ and HEL- B cells, we showed that in vivo latency was restricted to HEL- B cells while the two populations were equally sensitive to the virus in vitro. Moreover, MuHV-4 induced two waves of B cell activation. While the first wave was characterized by a general B cell activation, as shown by HEL+ and HEL- B cells expansion and upregulation of CD69 expression, the second wave was restricted to the HEL- population, which acquired germinal center (GC) and plasma cell phenotypes. Antigenic stimulation of HEL+ B cells led to the development of HEL+ GC B cells where latent infection remained undetectable, indicating that MuHV-4 does not benefit from acute B cell responses to establish latency in non-virus specific B cells but relies on other mechanisms of the humoral response. These data support a model in which the establishment of latency in B cells by γ-herpesviruses is not stochastic in terms of BCR specificity and is tightly linked to the formation of GCs.
Idioma originalEnglish
Número do artigoe1004269
RevistaPLoS Pathogens
Número de emissão7
Estado da publicaçãoPublicado - 31 jul. 2014
Publicado externamenteSim

Impressão digital

Mergulhe nos tópicos de investigação de “Establishment of murine gammaherpesvirus latency in b cells is not a stochastic event“. Em conjunto formam uma impressão digital única.