MX2 is an interferon-induced inhibitor of HIV-1 infection

Melissa Kane, Shalini S. Yadav, Julia Bitzegeio, Sebla B. Kutluay, Trinity Zang, Sam J. Wilson, John W. Schoggins, Charles M. Rice, Masahiro Yamashita, Theodora Hatziioannou, Paul D. Bieniasz

Research output: Contribution to journalArticle

237 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)563-566
Number of pages4
JournalNature
Volume502
Issue number7472
DOIs
StatePublished - 2013

Fingerprint

Orthomyxoviridae
Interferons
HIV Infections
HIV-1
Interferon Type I
Cell Nucleus Active Transport
Aptitude
Permissiveness
Lentivirus
Terminal Repeat Sequences
Capsid
DNA
Capsid Proteins
RNA Interference
Transcriptome
Cell Division
Reverse Transcription

ASJC Scopus subject areas

  • General

Cite this

Kane, M., Yadav, S. S., Bitzegeio, J., Kutluay, S. B., Zang, T., Wilson, S. J., ... Bieniasz, P. D. (2013). MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature, 502(7472), 563-566. https://doi.org/10.1038/nature12653

MX2 is an interferon-induced inhibitor of HIV-1 infection. / Kane, Melissa; Yadav, Shalini S.; Bitzegeio, Julia; Kutluay, Sebla B.; Zang, Trinity; Wilson, Sam J.; Schoggins, John W.; Rice, Charles M.; Yamashita, Masahiro; Hatziioannou, Theodora; Bieniasz, Paul D.

In: Nature, Vol. 502, No. 7472, 2013, p. 563-566.

Research output: Contribution to journalArticle

Kane, M, Yadav, SS, Bitzegeio, J, Kutluay, SB, Zang, T, Wilson, SJ, Schoggins, JW, Rice, CM, Yamashita, M, Hatziioannou, T & Bieniasz, PD 2013, 'MX2 is an interferon-induced inhibitor of HIV-1 infection', Nature, vol. 502, no. 7472, pp. 563-566. https://doi.org/10.1038/nature12653
Kane M, Yadav SS, Bitzegeio J, Kutluay SB, Zang T, Wilson SJ et al. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature. 2013;502(7472):563-566. https://doi.org/10.1038/nature12653
Kane, Melissa ; Yadav, Shalini S. ; Bitzegeio, Julia ; Kutluay, Sebla B. ; Zang, Trinity ; Wilson, Sam J. ; Schoggins, John W. ; Rice, Charles M. ; Yamashita, Masahiro ; Hatziioannou, Theodora ; Bieniasz, Paul D. / MX2 is an interferon-induced inhibitor of HIV-1 infection. In: Nature. 2013 ; Vol. 502, No. 7472. pp. 563-566.
@article{19f74d14fd0b46109ec83f44a82508d9,
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.",
author = "Melissa Kane and Yadav, {Shalini S.} and Julia Bitzegeio and Kutluay, {Sebla B.} and Trinity Zang and Wilson, {Sam J.} and Schoggins, {John W.} and Rice, {Charles M.} and Masahiro Yamashita and Theodora Hatziioannou and Bieniasz, {Paul D.}",
year = "2013",
doi = "10.1038/nature12653",
language = "English (US)",
volume = "502",
pages = "563--566",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7472",

}

TY - JOUR

T1 - MX2 is an interferon-induced inhibitor of HIV-1 infection

AU - Kane, Melissa

AU - Yadav, Shalini S.

AU - Bitzegeio, Julia

AU - Kutluay, Sebla B.

AU - Zang, Trinity

AU - Wilson, Sam J.

AU - Schoggins, John W.

AU - Rice, Charles M.

AU - Yamashita, Masahiro

AU - Hatziioannou, Theodora

AU - Bieniasz, Paul D.

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84886949134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886949134&partnerID=8YFLogxK

U2 - 10.1038/nature12653

DO - 10.1038/nature12653

M3 - Article

VL - 502

SP - 563

EP - 566

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7472

ER -