The interferon-inducible MxB protein inhibits HIV-1 infection.
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.
Lady Davis Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Zhenlong
Z
Liu
Qinghua
Q
Pan
Shilei
S
Ding
Jin
J
Qian
Fengwen
F
Xu
Jinming
J
Zhou
Shan
S
Cen
Fei
F
Guo
Chen
C
Liang
D021984:Cyclophilin A / Q000378:metabolism*; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007372:Interferons / Q000276:immunology*; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D020125:Mutation, Missense; D064547:Myxovirus Resistance Proteins / Q000378:metabolism*; D012641:Selection, Genetic; D016662:Virus Integration / Q000276:immunology*
D016655:HIV Core Protein p24; C579068:MX2 protein, human; D050505:Mutant Proteins; D064547:Myxovirus Resistance Proteins; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D007372:Interferons; D021984:Cyclophilin A