RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

Abstract

Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle.

Restricting retrotransposons: a review

“…In humans, MOV10 associates with APOBEC3 proteins and components of RISC in SGs and PBs [ 156 , 228 ]. Several groups examined the role of MOV10 in limiting HIV-1 replication but results were conflicted [ 229 – 233 ]. However, MOV10 strongly inhibits all human non-LTR retrotransposons in cell culture, consistent with its subcellular colocalization with L1 ORF1p in cytoplasmic granules, co-immunoprecipitation (co-IP) with the L1 RNP, and binding of L1 transcripts [ 232 , 234 – 236 ].…”

Elucidating the in vivo interactome of HIV-1 RNA by hybridization capture and mass spectrometry

“…This RNA-protein interaction helps the unspliced transcript evade surveillance mechanisms for degradation 4 , 6 and facilitates its export by the alternative Rev/CRM1-dependent nuclear export pathway 7 . Furthermore, Rev has been shown to recruit host proteins of diverse functions, including; nuclear matrix protein MATR3 8 , nonsense-mediated decay protein UPF1 9 , and RNA helicases DDX1 and MOV10 10 , 11 . Following nuclear export, the unspliced transcript can be incorporated into a variety of ribonucleoprotein complexes (RNPs).…”

Cellular RNA Helicases Support Early and Late Events in Retroviral Replication

“…In unresolved controversy, independent research identified siRNA downregulation of endogenous MOV10 did not change virion production and considered endogenous MOV10 acts as cofactor (Arjan-Odedra et al, 2012). In aggregate, modulation of MOV10 incurs an imbalance in HIV RNP activity, consistent with indirect and possibly beneficial effect on biogenesis of infectious HIV (Huang et al, 2015).…”