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.2018-03-152018-03-152014-08Reese, T. A., Wakeman, B. S., Choi, H. S., Hufford, M. M., Huang, S. C., Zhang, X., … Virgin, H. W. (2014). Helminth Infection Reactivates Latent γ-herpesvirus Via Cytokine Competition at a Viral Promoter. Science (New York, N.Y.), 345(6196), 573–577. http://doi.org/10.1126/science.1254517https://hdl.handle.net/1805/15574Mammals 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.en-USPublisher PolicyGammaherpesvirinaeHerpesvirus 8 -- HumanInterferon-gammaInterleukin-4Schistosoma mansoniVirus ActivationArticle