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Distinct patterns of IFITM-mediated restriction of filoviruses,SARS coronavirus,and influenza A virus
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نویسنده
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huang i.-c. ,bailey c.c. ,weyer j.l. ,radoshitzky s.r. ,becker m.m. ,chiang j.j. ,brass a.l. ,ahmed a.a. ,chi x. ,dong l. ,longobardi l.e. ,boltz d. ,kuhn j.h. ,elledge s.j. ,bavari s. ,denison m.r. ,choe h. ,farzan m.
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منبع
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plos pathogens - 2011 - دوره : 7 - شماره : 1
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چکیده
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Interferon-inducible transmembrane proteins 1,2,and 3 (ifitm1,2,and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza a virus (iav) hemagglutinin (ha) protein. here we show that ifitm proteins restricted infection mediated by the entry glycoproteins (gp1,2) of marburg and ebola filoviruses (marv,ebov). consistent with these observations,interferon-β specifically restricted filovirus and iav entry processes. ifitm proteins also inhibited replication of infectious marv and ebov. we observed distinct patterns of ifitm-mediated restriction: compared with iav,the entry processes of marv and ebov were less restricted by ifitm3,but more restricted by ifitm1. moreover,murine ifitm5 and 6 did not restrict iav,but efficiently inhibited filovirus entry. we further demonstrate that replication of infectious sars coronavirus (sars-cov) and entry mediated by the sars-cov spike (s) protein are restricted by ifitm proteins. the profile of ifitm-mediated restriction of sars-cov was more similar to that of filoviruses than to iav. trypsin treatment of receptor-associated sars-cov pseudovirions,which bypasses their dependence on lysosomal cathepsin l,also bypassed ifitm-mediated restriction. however,ifitm proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. our data indicate that ifitm-mediated restriction is localized to a late stage in the endocytic pathway. they further show that ifitm proteins differentially restrict the entry of a broad range of enveloped viruses,and modulate cellular tropism independently of viral receptor expression.
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آدرس
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department of microbiology and molecular genetics,harvard medical school,new england primate research center,southborough,ma, United States, department of microbiology and molecular genetics,harvard medical school,new england primate research center,southborough,ma, United States, department of microbiology and molecular genetics,harvard medical school,new england primate research center,southborough,ma, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, departments of pediatrics and microbiology and immunology,elizabeth b. lamb center for pediatric research,vanderbilt university medical center,nashville,tn, United States, department of microbiology and molecular genetics,harvard medical school,new england primate research center,southborough,ma, United States, ragon institute of massachusetts general hospital,massachusetts institute of technology,harvard medical school,charlestown,ma, United States, department of pediatrics,harvard medical school,children's hospital,boston,ma, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, integrated research facility at fort detrick,national institute of allergy and infectious diseases,national institutes of health,national interagency biodefense campus,frederick,md,united states,tunnell consulting inc,king of prussia,pa, United States, department of genetics,brigham and women's hospital,howard hughes medical institute,harvard medical school,boston,ma, United States, us army medical research institute of infectious disease,national interagency biodefense campus,frederick,md, United States, departments of pediatrics and microbiology and immunology,elizabeth b. lamb center for pediatric research,vanderbilt university medical center,nashville,tn, United States, department of pediatrics,harvard medical school,children's hospital,boston,ma, United States, department of microbiology and molecular genetics,harvard medical school,new england primate research center,southborough,ma, United States
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Authors
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