HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

摘要: Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat Rev proteins essential host factors cyclin T1 (CCNT1) exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell than CCNT1 XPO1 affect HIV's postintegration stages, we studied HIV-1NL4-3 gene expression in NIH 3T3 cells modified constitutively express HIV-1-compatible versions of (3T3.CX cells). 3T3.CX supported both Rev-independent Rev-dependent produced relatively robust levels virus particles, confirming that represent the predominant these stages. Unexpectedly, however, were remarkably resistant virus-induced cytopathic effects observed human lines, which mapped protein Vif its apparent capacity induce G2/M cycle arrest. was able mediate rapid degradation APOBEC3G PPP2R5D regulatory B56 subunit PP2A phosphatase holoenzyme cells, thus demonstrating VifNL4-3's modulation can be functionally uncoupled some defined roles CUL5-dependent degradation. unable arrest nonhuman types, including primates, leading us propose one or more human-specific cofactors underpin Vif's ability modulate cycle.IMPORTANCE replication, hindering development a low-cost small-animal model for studying HIV/AIDS. Here, engineered otherwise-nonpermissive two dependency factors, (XPO1) We show rescue particle production but, unexpectedly, are completely effects. accessory Vif, induces prolonged followed by apoptosis cells. Combined, our results indicate additional govern HIV-1's cycle, with potential relevance pathogenesis people existing animal models.