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TMEM41B Is a Pan-flavivirus Host Factor

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954666/
https://www.ncbi.nlm.nih.gov/pubmed/33338421
http://dx.doi.org/10.1016/j.cell.2020.12.005
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author 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.
author_facet 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.
author_sort Hoffmann, H.-Heinrich
collection PubMed
description 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.
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spelling pubmed-79546662021-03-15 TMEM41B Is a Pan-flavivirus Host Factor 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 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. Elsevier Inc. 2021-01-07 2020-12-09 /pmc/articles/PMC7954666/ /pubmed/33338421 http://dx.doi.org/10.1016/j.cell.2020.12.005 Text en © 2020 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
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.
TMEM41B Is a Pan-flavivirus Host Factor
title TMEM41B Is a Pan-flavivirus Host Factor
title_full TMEM41B Is a Pan-flavivirus Host Factor
title_fullStr TMEM41B Is a Pan-flavivirus Host Factor
title_full_unstemmed TMEM41B Is a Pan-flavivirus Host Factor
title_short TMEM41B Is a Pan-flavivirus Host Factor
title_sort tmem41b is a pan-flavivirus host factor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954666/
https://www.ncbi.nlm.nih.gov/pubmed/33338421
http://dx.doi.org/10.1016/j.cell.2020.12.005
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