Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors.
Hans-Heinrich HoffmannWilliam M SchneiderFrancisco J Sánchez RiveraJoseph M LunaAlison W AshbrookYadira M Soto-FelicianoAndrew A LealJérémie Le PenInna Ricardo-LaxEleftherios MichailidisYuan HaoAnsgar F StenzelAvery PeaceC David AllisScott W LoweMargaret R MacDonaldJohn T PoirierCharles M RicePublished in: bioRxiv : the preprint server for biology (2020)
Focused CRISPR screens targeting host factors in the SARS-CoV-2 interactome were performed for SARS-CoV-2, HCoV-229E, HCoV-NL63, and HCoV-OC43 coronaviruses.Focused interactome CRISPR screens achieve higher resolution compared to genome-wide screens, leading to the identification of critical factors missed by the latter.Parallel CRISPR screens against multiple coronaviruses uncover host factors and pathways with pan-coronavirus and virus-specific functional roles.The number of host proteins that interact with a viral bait protein is not proportional to the number of functional interactors.Novel SARS-CoV-2 host factors are expressed in relevant cell types in the human airway.