PACS1 is an HIV-1 cofactor that functions in Rev-mediated nuclear export of viral RNA

HIV-1 is dependent upon cellular proteins to mediate the many processes required for viral replication. One such protein, PACS1, functions to localize Furin to the trans-Golgi network where Furin cleaves HIV-1 gp160 Envelope into gp41 and gp120. We show here that PACS1 also shuttles between the nucleus and cytoplasm, associates with the viral Rev protein and its cofactor CRM1, and contributes to nuclear export of viral transcripts. PACS1 appears specific to the Rev-CRM1 pathway and not other retroviral RNA export pathways. Over-expression of PACS1 increases nuclear export of unspliced viral RNA and significantly increases p24 expression in HIV-1-infected Jurkat CD4(+) T cells. SiRNA depletion and over-expression experiments suggest that PACS1 may promote trafficking of HIV-1 GagPol RNA to a pathway distinct from that of translation on polyribosomes.