TF protein of Sindbis virus antagonizes host type I interferon responses in a palmitoylation-dependent manner

Sindbis virus (SINV) produces the small membrane protein TF from the 6K gene via a (−1) programmed ribosomal frameshifting. While several groups have shown that TF-deficient virus exhibits reduced virulence, mechanism(s) by which this occurs remain unknown. Here, we demonstrate a role for TF in antagonizing the host interferon response. Using wild-type and type 1 interferon receptor-deficient mice and primary cells derived from these animals, we show that TF controls the induction of the host interferon responses at early times during infection. Loss of TF production leads to elevated interferon and a concurrent reduction in viral loads with a loss of pathogenicity. Palmitoylation of TF has been shown to be important for particle assembly and morphology. We find that palmitoylation of TF also contributes to the ability of TF to antagonize host interferon responses as dysregulated palmitoylation of TF reduces virulence in a manner similar to loss of TF.