title: Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection.
abstract: Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1), these include widely expressed restriction factors, such as APOBEC3 proteins, TRIM5-α, BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN). Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like, IFN-induced myxovirus resistance 2 (MX2, also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-α-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested, has equivalent or reduced effects on divergent simian immunodeficiency viruses, and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late post-entry step, with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally, human MX1 (also known as MXA), a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus, does not affect HIV-1, whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.
authors.affiliation: Department of Infectious Diseases, King's College London, London SE1 9RT, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Goujon
authors.forename: Olivier
authors.initials: O
authors.lastname: Moncorgé
authors.forename: Hélène
authors.initials: H
authors.lastname: Bauby
authors.forename: Tomas
authors.initials: T
authors.lastname: Doyle
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Ward
authors.forename: Torsten
authors.initials: T
authors.lastname: Schaller
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hué
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
authors.forename: Reiner
authors.initials: R
authors.lastname: Schulz
authors.forename: Michael H
authors.initials: MH
authors.lastname: Malim
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000821:virology; D002478:Cells, Cultured; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007372:Interferons / Q000276:immunology*; D064547:Myxovirus Resistance Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription / Q000235:genetics; D013045:Species Specificity; D013379:Substrate Specificity; D016662:Virus Integration; D014779:Virus Replication
chemical_list: C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D012367:RNA, Viral; D007372:Interferons
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