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Cell Host Microbe. 2013 Oct 16;14(4):398-410. doi: 10.1016/j.chom.2013.08.015. Epub 2013 Sep 19.

The interferon-inducible MxB protein inhibits HIV-1 infection.

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1
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.

Abstract

The interferon-inducible myxovirus resistance (Mx) proteins play important roles in combating a wide range of virus infections. MxA inhibits many RNA and DNA viruses, whereas the antiviral activity of MxB is less well established. We find that human MxB inhibits HIV-1 infection by reducing the level of integrated viral DNA. Passaging HIV-1 through MxB-expressing cells allowed the evolution of a mutant virus that escapes MxB restriction. HIV-1 escapes MxB restriction by mutating the alanine residue at position 88 in the viral capsid protein (CA), with a consequent loss of CA interaction with the host peptidylprolyl isomerase cyclophilin A (CypA), suggesting a role for CypA in MxB restriction. Consistent with this, MxB associates with CypA, and shRNA-mediated CypA depletion or cyclosporine A treatment resulted in the loss of MxB inhibition of HIV-1. Taken together, we conclude that human MxB protein inhibits HIV-1 DNA integration by a CypA-dependent mechanism.

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PMID:
24055605
DOI:
10.1016/j.chom.2013.08.015
[Indexed for MEDLINE]
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