HIV-1 and M-PMV RNA Nuclear Export Elements Program Viral Genomes for Distinct Cytoplasmic Trafficking Behaviors

摘要: Retroviruses encode cis-acting RNA nuclear export elements that override retention of intron-containing viral mRNAs including the full-length, unspliced genomic RNAs (gRNAs) packaged into assembling virions. The HIV-1 Rev-response element (RRE) recruits cellular receptor CRM1 (also known as exportin-1/XPO1) using protein Rev, while simple retroviruses constitutive transport (CTEs) directly recruit components NXF1(Tap)/NXT1(p15) mRNA machinery. How gRNA is linked to trafficking machineries in cytoplasm upstream virus particle assembly unknown. Here we used long-term (>24 h), multicolor live cell imaging visualize export, translation, cytoplasmic trafficking, and production single cells. We show RRE regulates unique, en masse, Rev- CRM1-dependent “burst-like” transitions from nucleus flood a non-localized fashion. By contrast, CTE derived Mason-Pfizer monkey (M-PMV) links gRNAs microtubules cytoplasm, driving them cluster markedly centrosome forms pericentriolar core microtubule-organizing center (MTOC). Adding each selected heterologous was sufficient confer distinct behavior, directing Rev/CRM1 or NXF1/NXT1 modules site-specific tethering strategy. Moreover, multiple CTEs per transcript enhanced MTOC targeting, suggesting cooperative mechanism microtubules. Combined, these results reveal striking, unexpected features retroviral nucleocytoplasmic demonstrate roles for extend beyond pores impact distribution cytoplasm.