The major human immunodeficiency virus type 2 (HIV-2) packaging signal is present on all HIV-2 RNA species: Cotranslational RNA encapsidation and limitation of Gag protein confer specificity

Deletion of a region of the human immunodeficiency virus type 2 (HIV-2) 5' leader RNA reduces genomic RNA encapsidation to about 5% that of wild-type virus with no defect in viral protein production but severely limits virus spread in Jurkat T cells, indicating that this region contains a major cis- acting encapsidation signal, or psi (psi). Being upstream of the major spli ce donor, it is present on all viral transcripts. We have shown that HIV-2 selects its genomic RNA for encapsidation cotranslationally, rendering wild -type HIV-2 unable to encapsidate vector RNAs in trans. Virus with psi dele ted, however, encapsidates an HIV-2 vector, demonstrating competition for G ag protein. HIV-2 overcomes the lack of packaging signal location specifici ty by two novel mechanisms, cotranslational packaging and competition for l imiting Gag polyprotein.