Helminth Infection Reactivates Latent γ-herpesvirus Via Cytokine Competition at a Viral Promoter. Mus musculus

Mammals are co-infected 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 gammaherpesvirus infection in vivo. IL-4 promoted viral replication and blocked the antiviral effects of interferon-g (IFNg) 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 IFNg reactivated latent murine gammaherpesvirus 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. Overall design: All of the RNA from virus-pos cells and 50 ng of RNA from virus-neg cells was prepared for RNA-seq using ScriptSeq v2 RNA-seq library preparation kit (Epicentre). Index Primers (Epicentre) were added and samples underwent Duplex-Specific thermostable nuclease (DSN) (Evrogen) treatment to remove ribosomal RNA. Samples were pooled and sequenced on HiSeq.