The interferon-inducible MxB protein inhibits HIV-1 infection

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclophilin A / metabolism*
  • HIV Core Protein p24 / genetics
  • HIV Core Protein p24 / immunology
  • HIV-1 / immunology*
  • HIV-1 / physiology*
  • Host-Pathogen Interactions*
  • Humans
  • Immune Evasion
  • Interferons / immunology*
  • Mutant Proteins / genetics
  • Mutant Proteins / immunology
  • Mutation, Missense
  • Myxovirus Resistance Proteins / metabolism*
  • Selection, Genetic
  • Virus Integration / immunology*

Substances

  • HIV Core Protein p24
  • MX2 protein, human
  • Mutant Proteins
  • Myxovirus Resistance Proteins
  • p24 protein, Human Immunodeficiency Virus Type 1
  • Interferons
  • Cyclophilin A