Letter | Published:

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

Nature volume 502, pages 563566 (24 October 2013) | Download Citation


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 IFN1,2. 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 cells3,4. 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.

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We thank members of The Rockefeller University Genomics Resource Center for assistance with the microarray experiments and members of the Bieniasz laboratory for discussion and advice. This work was supported by grants from the National Institutes of Health; R37AI64003 (to P.D.B.), R01AI078788 (to T.H.) R01AI100720 (to M.Y.), AI091707 to C.M.R., AI057158 (to I. Lipkin, Northeast Biodefense Center, subcontracted to C.M.R.) and DK095031 to J.W.S., the Greenberg Medical Research Institute and the Starr Foundation (C.M.R.) and by the Howard Hughes Medical Institute.

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Author notes

    • Shalini S. Yadav
    • , Sam J. Wilson
    •  & John W. Schoggins

    Present addresses: University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9048, USA (J.W.S.); MRC Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK (S.J.W.); Weill Cornell Medical College, 525 East 68th street, New York, New York 10025, USA (S.S.Y.).


  1. Aaron Diamond AIDS Research Center, New York, New York 10016, USA

    • Melissa Kane
    • , Shalini S. Yadav
    • , Julia Bitzegeio
    • , Sebla B. Kutluay
    • , Trinity Zang
    • , Sam J. Wilson
    • , Masahiro Yamashita
    • , Theodora Hatziioannou
    •  & Paul D. Bieniasz
  2. Laboratory of Retrovirology, The Rockefeller University, New York, New York 10065, USA

    • Melissa Kane
    • , Shalini S. Yadav
    • , Julia Bitzegeio
    • , Sebla B. Kutluay
    • , Trinity Zang
    • , Sam J. Wilson
    •  & Paul D. Bieniasz
  3. Howard Hughes Medical Institute, New York, New York 10016, USA

    • Shalini S. Yadav
    • , Trinity Zang
    • , Sam J. Wilson
    •  & Paul D. Bieniasz
  4. Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10065, USA

    • John W. Schoggins
    •  & Charles M. Rice


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M.K., S.S.Y., J.B., S.B.K., T.Z. and S.J.W. designed and executed the experiments and analysed the data. J.W.S. and C.M.R. provided an interferon-stimulated gene library and advice. M.Y. provided reagents and advice. T.H. provided reagents and advice and supervised the work. P.D.B. conceived the study, supervised the work and wrote the paper, with additional input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Paul D. Bieniasz.

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