气候变化领域集成服务门户(CCPortal): Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy

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DOI	10.1073/pnas.2104759118
	Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy
	Anderson D.E.; Cui J.; Ye Q.; Huang B.; Tan Y.; Jiang C.; Zu W.; Gong J.; Liu W.; Kim S.Y.; Yan B.G.; Sigmundsson K.; Lim X.F.; Ye F.; Niu P.; Irving A.T.; Zhang H.; Tang Y.; Zhou X.; Wang Y.; Tan W.; Wang L.-F.; Tan X.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:39
英文摘要	Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, Pteropus alecto. We used the complementary RNAi and CRISPR libraries to interrogate P. alecto cells for infection with two different viruses: Mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antiviral therapy; Bat; CRISPR; RNAi
语种	英语
scopus关键词	antivirus agent; formate tetrahydrofolate ligase; formyl-methenyl-methylenetetrahydrofolate synthetase; hydrolase; methylenetetrahydrofolate dehydrogenase; minor histocompatibility antigen; multienzyme complex; animal; bat; cell line; drug therapy; genetics; human; pandemic; pathogenicity; RNA virus; virology; virus replication; Aminohydrolases; Animals; Antiviral Agents; Cell Line; Chiroptera; COVID-19; Formate-Tetrahydrofolate Ligase; Humans; Methylenetetrahydrofolate Dehydrogenase (NADP); Minor Histocompatibility Antigens; Multienzyme Complexes; Pandemics; RNA Viruses; SARS-CoV-2; Virus Replication
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238373
作者单位	Programme in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, 169857, Singapore; MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, 100084, China; National Health Commission Key Laboratory of Biosafety, Ministry of Health, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China; Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27708, United States; Programme in Cardiovascular and Metabolic Disorders, Duke-National University, Singapore Medical School, Singapore, 169857, Sing...
推荐引用方式 GB/T 7714	Anderson D.E.,Cui J.,Ye Q.,et al. Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy[J],2021,118(39).
APA	Anderson D.E..,Cui J..,Ye Q..,Huang B..,Tan Y..,...&Tan X..(2021).Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.Proceedings of the National Academy of Sciences of the United States of America,118(39).
MLA	Anderson D.E.,et al."Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy".Proceedings of the National Academy of Sciences of the United States of America 118.39(2021).