SARS-CoV-2 Variants of Concern Hijack IFITM2 for Efficient Replication in Human Lung Cells
Rayhane Nchioua, Annika Schundner, Dorota Kmieć, Caterina Prelli Bozzo, Fabian Zech, Lennart Koepke, Alexander Graf, Stefan Krebs, Helmut Blum, Manfred Frick, Konstantin M. J. Sparrer, Frank Kirchhoff
Abstract
Recent data indicate that SARS-CoV-2 requires endogenously expressed IFITM proteins for efficient infection. However, the results were obtained with an early SARS-CoV-2 isolate. Thus, it remained to be determined whether IFITMs are also important cofactors for infection of emerging SARS-CoV-2 VOCs that outcompeted the original strains in the meantime. This includes the Omicron VOC, which currently dominates the pandemic. Here, we show that depletion of endogenous IFITM2 expression almost entirely prevents productive infection of Alpha, Beta, Gamma, Delta, and Omicron SARS-CoV-2 VOCs in human lung cells. In addition, an antibody targeting the N terminus of IFITM2 inhibited SARS-CoV-2 VOC replication in iPSC-derived alveolar epithelial type II cells. Our results show that SARS-CoV-2 VOCs, including the currently dominant Omicron variant, are strongly dependent on IFITM2 for efficient replication, suggesting a key proviral role of IFITMs in viral transmission and pathogenicity.