NONRECIPROCAL PACKAGING OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 RNA - A POSSIBLE ROLE FOR THE P2 DOMAIN OF GAG IN RNA ENCAPSIDATION

The ability of human immunodeficiency virus types 1 (HIV-1) and 2 (HIV -2) to cross-package each other's RNA was investigated by cotransfecti ng helper virus constructs with vectors derived from both viruses from which the gag and pal sequences had been removed. HIV-1 was able to p ackage both HIV-1 and HIV-2 vector RNA. The unspliced HIV-1 vector RNA was packaged preferentially over spliced RNA; however, unspliced and spliced HIV-2 vector RNA were packaged in proportion to their cytoplas mic concentrations. The HIV-2 helper virus was unable to package the H IV-1 vector RNA, indicating a nonreciprocal RNA packaging relationship between these two lentiviruses. Chimeric proviruses based on HIV-2 we re constructed to identify the regions of the HIV-1 Gag protein confer ring RNA-packaging specificity for the HIV-1 packaging signal. Two chi meric viruses were constructed in which domains within the HIV-2 gag g ene were replaced by the corresponding domains in HIV-1, and the abili ty of the chimeric proviruses to encapsidate an HN-l-based vector was studied. Wild-type HIV-2 was unable to package the HIV-1-based vector; however, replacement of the HIV-2 nucleocapsid by that of HIV-1 gener ated a virus with normal protein processing which could package the HI V-1-based vector. The chimeric viruses retained the ability to package HIV-2 genomic RNA, providing further evidence for a lack of reciproci ty in RNA-packaging ability between the HIV-1 and HIV-2 nucleocapsid p roteins, Inclusion of the p2 domain of HIV-1 Gag in the chimera signif icantly enhanced packaging.