Journal Article

Nuclear pore heterogeneity influences HIV-1 infection and the antiviral activity of MX2

Rebensburg, Stephanie V, Takata, Matthew A, Yamashita, Masahiro, Kvaratskhelia, Mamuka, Kane, Melissa, Bieniasz, Paul D, Zang, Trinity M

2018

Overview

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.

• Publisher: eLife Sciences Publications, Ltd,eLife Sciences Publications Ltd
• Subject: Antiviral Agents - metabolism / Capsid Proteins - metabolism / Cell Biology / Cell Line / HIV / HIV Infections - pathology / HIV Infections - virology / HIV-1 - growth & development / HIV-1 - immunology / Humans / integration / Microbiology and Infectious Disease / Myxovirus Resistance Proteins - metabolism / nuclear import / Nuclear Pore - metabolism / Nuclear Pore Complex Proteins - metabolism / nucleoporin / Protein Binding