Browsing by Author "Murray, P.J."

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    Helminth infection reactivates latent γ-herpesvirus via cytokine competition at a viral promoter
    (American Association for the Advancement of Science, 2014-08) Reese, T.A.; Wakeman, B.S.; Choi, H.S.; Hufford, M.M.; Huang, S.C.; Zhang, X.; Buck, M.D.; Jezewski, A.; Kambal, A.; Liu, C.Y.; Goel, G.; Murray, P.J.; Xavier, R.J.; Kaplan, M.H.; Renne, R.; Speck, S.H.; Artyomov, M.N.; Pearce, E.J.; Virgin, H.W.; Pediatrics, School of Medicine
    Mammals are coinfected by multiple pathogens that interact through unknown mechanisms. We found that helminth infection, characterized by the induction of the cytokine interleukin-4 (IL-4) and the activation of the transcription factor Stat6, reactivated murine γ-herpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-γ (IFNγ) by inducing Stat6 binding to the promoter for an important viral transcriptional transactivator. IL-4 also reactivated human Kaposi's sarcoma-associated herpesvirus from latency in cultured cells. Exogenous IL-4 plus blockade of IFNγ reactivated latent murine γ-herpesvirus infection in vivo, suggesting a "two-signal" model for viral reactivation. Thus, chronic herpesvirus infection, a component of the mammalian virome, is regulated by the counterpoised actions of multiple cytokines on viral promoters that have evolved to sense host immune status.