title: Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11.
abstract: In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway. However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Manqing
authors.initials: M
authors.lastname: Li
authors.forename: Elaine
authors.initials: E
authors.lastname: Kao
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.forename: Hilary
authors.initials: H
authors.lastname: Sandig
authors.forename: Kirsten
authors.initials: K
authors.lastname: Limmer
authors.forename: Mariana
authors.initials: M
authors.lastname: Pavon-Eternod
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Jones
authors.forename: Sebastien
authors.initials: S
authors.lastname: Landry
authors.forename: Tao
authors.initials: T
authors.lastname: Pan
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Weitzman
authors.forename: Michael
authors.initials: M
authors.lastname: David
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D003062:Codon / Q000235:genetics* / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000235:genetics* / Q000276:immunology; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription; D013045:Species Specificity; D013379:Substrate Specificity; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics*; D016662:Virus Integration
chemical_list: D003062:Codon; D009687:Nuclear Proteins; D012367:RNA, Viral; C576668:SLFN11 protein, human; D014764:Viral Proteins; D012343:RNA, Transfer