RESEARCH AREAS

Viruses hijack the host translation machinery to synthesize their own proteins. To effectively compete with host transcripts for the translation machinery, viruses employ various mechanisms that enhance viral translation while inhibiting host translation. This selective translation not only ensures efficient synthesis of viral proteins, but also suppresses antiviral responses by limiting host protein synthesis. Our recent research has shown that SARS-CoV-2 infection shuts down host translation, largely due to the nonstructural protein NSP14. Furthermore, this translation inhibition strategy may be an effective viral immune evasion strategy employed by SARS-CoV-2 to evade the type I interferon (IFN-I) antiviral response. We will focus on understanding how translational regulations induced by viruses such as SARS-CoV-2, Zika virus, and eastern equine encephalitis virus play pivotal roles in pathogenesis and viral immune evasion.

On the flip side,  as viruses completely depend on host translation for viral protein synthesis, a common cellular response to viral infection is translation inhibition. IFN-I inhibits global translation to establish an antiviral state in host cells primarily by inducing interferon-stimulated genes (ISGs).  In a recently accepted manuscript, we found that the ISG-encoded antiviral protein viperin inhibits the replication of flaviviruses by limiting viral translation. We demonstrated that viperin and its enzymatic product 3'-deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) induce ribosome collision-dependent translation inhibition to limit viral replication.  However, how viperin/ddhCTP induce ribosome collisions remains unknown. We will focus on understanding how ribosome collisions are induced during the antiviral response and how such cellular stress can benefit host cells against pathogens.