Letter | Published:

Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection

Nature volume 502, pages 559562 (24 October 2013) | Download Citation


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 factors1, such as APOBEC3 proteins2, TRIM5-α3, BST2 (refs 4, 5) and SAMHD1 (refs 6, 7), as well as additional factors that are stimulated by type 1 interferon (IFN)8,9,10,11,12,13,14. 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 virus15,16, 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.

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Gene Expression Omnibus

Data deposits

The microarray methods and data are available under Gene Expression Omnibus GEO accession number GSE46599.


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We wish to thank L. Apolonia, A. Cimarelli, B. Hahn, T. Hatziioannou, J. Kappes, P. Mangeot, S. Papaioannou, N. Parrish, N. Sherer and C. Swanson for the provision of reagents and for discussions, and M. Mirza, E. Papouli, Q. Oscar Y. Li and G. Pacini for technical assistance. This work was supported by the UK Medical Research Council, the National Institutes of Health (DA033773), the European Commission’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. PIEF-GA-2009-237501 (to C.G.), a Wellcome Trust Research Training Fellowship (to T.D.) and the Department of Health via a National Institute for Health Research comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust.

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  1. Department of Infectious Diseases, King’s College London, London SE1 9RT, UK

    • Caroline Goujon
    • , Hélène Bauby
    • , Tomas Doyle
    • , Christopher C. Ward
    • , Torsten Schaller
    •  & Michael H. Malim
  2. Section of Virology, Division of Infectious Diseases, Imperial College London, London W2 1PG, UK

    • Olivier Moncorgé
    •  & Wendy S. Barclay
  3. Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London WC1 6RT, UK

    • Stéphane Hué
  4. Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK

    • Reiner Schulz


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C.G. and M.H.M. designed the study and wrote the manuscript. C.G. carried out the experiments. O.M. and W.S.B. designed and carried out the influenza A virus experiment. O.M., H.B., T.D., C.C.W., T.S. and S.H. provided technical assistance. R.S. performed the microarray analysis. All authors read and approved the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Michael H. Malim.

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