Murine leukemia virus glycosylated Gag (gPr80gag) facilitates interferon-sensitive virus release through lipid rafts

Murine leukemia viruses encode a unique form of Gag polyprotein, gPr80(gag) or glyco-gag. Translation of this protein is initiated from full length viral mRNA at an upstream initiation site in the same reading frame as Pr65(gag), the precursor for internal structural (Gag) proteins. Whereas gPr80(gag) is evolutionarily conserved among gammaretroviruses, its mechanism of action has been unclear, although it facilitates virus production at a late assembly or release step. Here, it is shown that gPr80(gag) facilitates release of Moloney murine leukemia virus (M-MuLV) from cells along an IFN-sensitive pathway. In particular, gPr80(gag)-facilitated release occurs through lipid rafts, because gPr80(gag)-negative M-MuLV has a lower cholesterol content, is less sensitive to inhibition of release by the cholesterol-depleting agent M beta CD, and there is less Pr65(gag) associated with detergent-resistant membranes in mutant-infected cells. gPr80(gag) can also facilitate the release of HIV-1-based vector particles from human 293T cells.