TMEM41B is a pan-flavivirus host factor Journal Article

Authors: Hoffmann, H. H.; Schneider, W. M.; Rozen-Gagnon, K.; Miles, L. A.; Schuster, F.; Razooky, B.; Jacobson, E.; Wu, X.; Yi, S.; Rudin, C. M.; MacDonald, M. R.; McMullan, L. K.; Poirier, J. T.; Rice, C. M.
Article Title: TMEM41B is a pan-flavivirus host factor
Abstract: 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. © 2020 Elsevier Inc. 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. © 2020 Elsevier Inc.
Keywords: autophagy; membrane remodeling; coronavirus; crispr; flavivirus; flavivirus replication complex; tmem41b; vmp1
Journal Title: Cell
Volume: 184
Issue: 1
ISSN: 0092-8674
Publisher: Cell Press  
Date Published: 2021-01-07
Start Page: 133
End Page: 148.e20
Language: English
DOI: 10.1016/j.cell.2020.12.005
PUBMED: 33338421
PROVIDER: scopus
PMCID: PMC7954666
Notes: Article -- Export Date: 1 February 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Charles Rudin
    356 Rudin
  2. Linde Anne Miles
    18 Miles