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Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication [Focused cell]

ABSTRACT: Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication [Focused cell]

PROVIDER: PRJNA715218 | ENA |

REPOSITORIES: ENA

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Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication [RNA-seq]

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Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication

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Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication

Project description:This SuperSeries is composed of the SubSeries listed below.

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Genome-scale CRISPR screen identifies TMEM41B as a critical host factor required for coronavirus replication [PigGeCKO]

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TMEM41B is a pan-flavivirus host factor

Project 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 (SNPs) present at nearly twenty percent 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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Genome-scale CRISPR screen identifies TMEM41B as a multi-function host factor required for coronavirus replication.

Project description: Not available

| S-EPMC8675922 | biostudies-literature

Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

Project description:The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS- CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan- coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.

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