Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) can restrict viral pathogens, but pro- and anti-viral activities have been reported for coronaviruses. Here, we show that artificial overexpression of IFITMs blocks SARS-CoV-2 infection. However, endogenous IFITM expression supports efficient infection of SARS-CoV-2 in human lung cells. Our results indicate that the SARS-CoV-2 Spike protein interacts with IFITMs and hijacks them for efficient viral infection. IFITM proteins were expressed and further induced by interferons in human lung, gut, heart and brain cells. IFITM-derived peptides and targeting antibodies inhibit SARS-CoV-2 entry and replication in human lung cells, cardiomyocytes and gut organoids. Our results show that IFITM proteins are cofactors for efficient SARS-CoV-2 infection of human cell types representing in vivo targets for viral transmission, dissemination and pathogenesis and are potential targets for therapeutic approaches. IFITM proteins can inhibit several viruses, but effects on SARS-CoV-2 infection are not well understood. Here, the authors show that endogenous IFITMs support SARS-CoV-2 infection in different in vitro models by binding spike and enhancing virus entry.
【저자키워드】 viral infection, Innate immunity, 【초록키워드】 viruses, SARS-CoV-2, Coronaviruses, Pathogenesis, spike, antibody, SARS-COV-2 infection, Infection, interferon, peptide, Brain, Replication, Protein, cells, human lung, virus entry, target, Viral transmission, organoids, anti-viral activity, dissemination, in vivo, expression, binding, Gut, cofactor, Support, therapeutic approaches, human lung cells, overexpression, viral pathogens, transmembrane protein, IFITM, human cell, in vitro model, block, Effect, reported, inhibit, interact, restrict, representing, were expressed, inhibit SARS-CoV-2, the SARS-CoV-2, 【제목키워드】 SARS-COV-2 infection, in vitro, Protein, virus inhibition, target, IFITM, promote,