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

273 Scopus citations

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
Pages (from-to)563-566
Number of pages4
JournalNature
Volume502
Issue number7472
DOIs
StatePublished - Oct 14 2013
Externally publishedYes

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    Kane, M., Yadav, S. S., Bitzegeio, J., Kutluay, S. B., Zang, T., Wilson, S. J., Schoggins, J. W., Rice, C. M., Yamashita, M., Hatziioannou, T., & 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