2. Academic Validation
  3. TMEM41B Is a Pan-flavivirus Host Factor

TMEM41B Is a Pan-flavivirus Host Factor

  • Cell. 2021 Jan 7;184(1):133-148.e20. doi: 10.1016/j.cell.2020.12.005.
H-Heinrich Hoffmann 1,  William M Schneider 1,  Kathryn Rozen-Gagnon 1,  Linde A Miles 2,  Felix Schuster 3,  Brandon Razooky 1,  Eliana Jacobson 1,  Xianfang Wu 1,  Soon Yi 1,  Charles M Rudin 4,  Margaret R MacDonald 1,  Laura K McMullan 5,  John T Poirier 6,  Charles M Rice 7
Affiliations

Affiliations

  • 1 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
  • 2 Human Oncology & Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 3 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA; Institute of Virology, Medical Faculty "Carl Gustav Carus", Technische Universität Dresden, Dresden, Germany.
  • 4 Druckenmiller Center for Lung Cancer Research and Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • 5 Virus Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers of Disease Control and Prevention, Atlanta, GA, USA.
  • 6 Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, NY, USA. Electronic address: john.poirier@nyulangone.org.
  • 7 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA. Electronic address: ricec@rockefeller.edu.
PMID: 33338421 DOI: 10.1016/j.cell.2020.12.005
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.

Keywords

CRISPR; TMEM41B; VMP1; autophagy; coronavirus; flavivirus; flavivirus replication complex; membrane remodeling.

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