Interleukin 21 Signaling in B Cells Is Required for Efficient Establishment of Murine Gammaherpesvirus Latency


Gammaherpesviruses establish life-long infection in B cells by taking advantage of the host immune response that is generated during primary infection. During initial infection, the immune system responds by inducing rapid proliferation of responding B cells during the germinal center reaction. This response is highly coordinated and relies on the interplay of multiple cell types. CD4 T helper cells are an important component of the germinal center reaction in that they communicate with B cells by providing both proliferation and survival signals. Gammaherpesviruses infect B cells that receive these signals, resulting in proliferation and survival of infected cells, allowing the virus to establish life-long infection. Here we show that interleukin 21 (IL-21), one of the signaling factors produced by CD4 T cells, is required for efficient establishment of infection in a mouse model of gammaherpesvirus infection. In the absence of IL-21 signaling, the viral load is markedly reduced and the composition of the infected cell population is altered to cell types that are less proliferative and produce less virus. These results demonstrate how gammaherpesviruses are able to take advantage of the immune response being generated against it to establish lifelong infection.


Vyšlo v časopise: Interleukin 21 Signaling in B Cells Is Required for Efficient Establishment of Murine Gammaherpesvirus Latency. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004831
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004831

Souhrn

Gammaherpesviruses establish life-long infection in B cells by taking advantage of the host immune response that is generated during primary infection. During initial infection, the immune system responds by inducing rapid proliferation of responding B cells during the germinal center reaction. This response is highly coordinated and relies on the interplay of multiple cell types. CD4 T helper cells are an important component of the germinal center reaction in that they communicate with B cells by providing both proliferation and survival signals. Gammaherpesviruses infect B cells that receive these signals, resulting in proliferation and survival of infected cells, allowing the virus to establish life-long infection. Here we show that interleukin 21 (IL-21), one of the signaling factors produced by CD4 T cells, is required for efficient establishment of infection in a mouse model of gammaherpesvirus infection. In the absence of IL-21 signaling, the viral load is markedly reduced and the composition of the infected cell population is altered to cell types that are less proliferative and produce less virus. These results demonstrate how gammaherpesviruses are able to take advantage of the immune response being generated against it to establish lifelong infection.


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