Grant: Travel Awards - Institute Community Support

Host innate immune response to viral infection often limits efficiency of viral oncolysis. Viruses rely on the host cell's translational machinery to propagate, while cells use the same machinery to mount immune response against viruses. Elucidating the translational regulation that occurs during viral-host interaction can yield novel targets that affect virus propagation, which could be used to readapt oncolytic viruses to infect cancer cells more efficiently. To address this, we performed ribosome profiling techniques to systematically identify host transcripts that are differentially translated during infection with three of the most clinically relevant oncolytic viruses: HSV1, reovirus, and vaccinia virus. Interestingly, genes that are related to the generation and function of the primary cilia are enriched in the screen. Knockdown of two representative hits, BBS9 and INPP5E, resulted in an enhanced virus infection in two cancer cell lines. The results so far suggest an unknown function of the primary cilia in host-virus interaction. Altogether, the work also proposes a complex but poorly understood interaction network at the translational level between host and virus that yields great potential in re-engineering oncolytic virus efficiency.