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Medical and health sciences
- Innate immunity
- Virology
Viruses are obligate intracellular parasites that hijack the host cell machinery for their replication. To combat viral diseases, it is crucial to understand how viruses interact with their hosts. For influenza viruses, genome-wide genetic screens have so far primarily revealed host factors that are involved in the early steps of infection, leaving much to learn about host-virus interactions at the late stages of infection. To address this shortcoming, we aim to develop an influenza virus-vectored intrabody screening platform to identify host cell factors that impact influenza A virus (IAV) infection. IAVs that encode intrabodies that target a host dependency factor (HDF) are expected to be counter-selected in a competition experiment with viruses that encode a neutral or restriction factor (RF) repressing nanobody, while IAVs that encode intrabodies that target viral RFs, will have a selective advantage in these competition experiments. In contrast to the genetic screens, our proposed method functions at the protein level only during infection, providing a novel angle that may enable us to identify new post-entry HDFs and RFs of IAV. The findings of this project will expand our knowledge about host-IAV interactions and may be instrumental in the generation of new antiviral drugs.