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Published on: December 29, 2015
TMEM41B Is a Pan-flavivirus Host Factor
H-Heinrich Hoffmann1, William M Schneider1, Kathryn Rozen-Gagnon1
1Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY, USA.
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.
Insights
Scientists identified TMEM41B as a crucial host factor for flavivirus replication. This protein is essential for viral RNA replication, and genetic variations in it can reduce infection rates.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Flaviviruses are a significant global health concern, causing outbreaks via mosquito and tick bites.
- Identifying host factors is critical for understanding and controlling viral infections.
Purpose of the Study:
- To identify host factors essential for flavivirus replication.
- To characterize the role of TMEM41B in the viral life cycle.
Main Methods:
- Genome-wide CRISPR-Cas9 loss-of-function screens were employed.
- Mechanistic studies were conducted to elucidate the function of TMEM41B.
Main Results:
- TMEM41B is required by all tested members of the Flaviviridae family and also by SARS-CoV-2.
- Single nucleotide polymorphisms in TMEM41B are associated with reduced flavivirus infection in East Asian populations.
- TMEM41B facilitates membrane curvature in viral RNA replication complexes.
Conclusions:
- TMEM41B is a critical host factor for replication across multiple virus families, including Flaviviridae and Coronaviridae.
- TMEM41B's role in membrane curvature is key to creating a protected environment for viral genome replication.
- Genetic variations in TMEM41B have implications for host susceptibility to flavivirus infections.
