title: MX2 is an interferon-induced inhibitor of HIV-1 infection.
abstract: HIV-1 replication can be inhibited by type I interferon (IFN), and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN. However, none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early, preintegration phases of the HIV-1 replication cycle in human cells. Here, by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-α at early steps of the HIV-1 replication cycle, we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-α. HIV-1 reverse transcription proceeds normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that are known, or suspected, to alter the nuclear import pathways used by HIV-1 confer resistance to MX2, whereas preventing cell division increases MX2 potency. Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
authors.affiliation: 1] Aaron Diamond AIDS Research Center, New York, New York 10016, USA [2] Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Kane
authors.forename: Shalini S
authors.initials: SS
authors.lastname: Yadav
authors.forename: Julia
authors.initials: J
authors.lastname: Bitzegeio
authors.forename: Sebla B
authors.initials: SB
authors.lastname: Kutluay
authors.forename: Trinity
authors.initials: T
authors.lastname: Zang
authors.forename: Sam J
authors.initials: SJ
authors.lastname: Wilson
authors.forename: John W
authors.initials: JW
authors.lastname: Schoggins
authors.forename: Charles M
authors.initials: CM
authors.lastname: Rice
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D021581:Active Transport, Cell Nucleus; D002213:Capsid / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D048348:Reverse Transcription; D059467:Transcriptome; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D050505:Mutant Proteins; D064547:Myxovirus Resistance Proteins