Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2.
HIV-1 accesses the nuclear DNA of interphase cells via a poorly defined process involving functional interactions between the capsid protein (CA) and nucleoporins (Nups). Here, we show that HIV-1 CA can bind multiple Nups, and that both natural and manipulated variation in Nup levels impacts HIV-1 infection in a manner that is strikingly dependent on cell-type, cell-cycle, and cyclophilin A (CypA). We also show that Nups mediate the function of the antiviral protein MX2, and that MX2 can variably inhibit non-viral NLS function. Remarkably, both enhancing and inhibiting effects of cyclophilin A and MX2 on various HIV-1 CA mutants could be induced or abolished by manipulating levels of the Nup93 subcomplex, the Nup62 subcomplex, NUP88, NUP214, RANBP2, or NUP153. Our findings suggest that several Nup-dependent 'pathways' are variably exploited by HIV-1 to target host DNA in a cell-type, cell-cycle, CypA and CA-sequence dependent manner, and are differentially inhibited by MX2.
['Kane|Melissa|M|http://orcid.org/0000-0002-4580-1210', 'Rebensburg|Stephanie V|SV|', 'Takata|Matthew A|MA|', 'Zang|Trinity M|TM|', 'Yamashita|Masahiro|M|', 'Kvaratskhelia|Mamuka|M|', 'Bieniasz|Paul D|PD|http://orcid.org/0000-0002-2368-3719']
D000998:Antiviral Agents D036022:Capsid Proteins D002460:Cell Line D015658:HIV Infections D015497:HIV-1 D006801:Humans D064547:Myxovirus Resistance Proteins D022022:Nuclear Pore D028861:Nuclear Pore Complex Proteins D011485:Protein Binding
nucleoporin HIV cell biology infectious disease integration microbiology nuclear import virus