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  • TMEM41B Is a Pan-flavivirus...
    Hoffmann, H.-Heinrich; Schneider, William M.; Rozen-Gagnon, Kathryn; Miles, Linde A.; Schuster, Felix; Razooky, Brandon; Jacobson, Eliana; Wu, Xianfang; Yi, Soon; Rudin, Charles M.; MacDonald, Margaret R.; McMullan, Laura K.; Poirier, John T.; Rice, Charles M.

    Cell, 01/2021, Volume: 184, Issue: 1
    Journal Article

    Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection, we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results, we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms present at nearly 20% in East Asian populations reduce flavivirus infection. Based on our mechanistic studies, we propose that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication. Display omitted •TMEM41B is required for flavivirus infection, but autophagy is not required•TMEM41B associates with flavivirus proteins and may facilitate cell membrane remodeling•TMEM41B single nucleotide polymorphisms reduce flavivirus infection•TMEM41B-deficiency confers a heightened innate immune response to flavivirus infection Hoffmann et al. determine that the transmembrane protein, TMEM41B, is required for infection by members of the Flaviviridae family of viruses. Loss of TMEM41B reduces viral RNA replication and increases innate immune activation in response to flavivirus infection. Thus, TMEM41B is a potential host target for antiviral therapeutics.