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

Kane, M. et al. (2013) MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature, 502(7472), pp. 563-566. (doi: 10.1038/nature12653)

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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.

Item Type:Articles (Letter)
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wilson, Professor Sam
Authors: 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., and Bieniasz, P.D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature
ISSN:0028-0836
ISSN (Online):1476-4687

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