The role of murine leukemia virus glycosated Gag protein in virus replication

Murine leukemia viruses (MuLVs) encode an alternate form of Gag protein in addition to the standard Gag precursor polyprotein, glycosylated Gag (glyco-gag or gPr80^gag). gPr80^gag contains additional amino-terminal peptides, and it is glycosylated. Until recently the function of gPr80^gag was unclear, but we have recently shown that gPr80^gag facilitates viral budding and release through lipid rafts. Glyco-gag mutant virus is less efficiently released from fibroblasts, mutant virus has lower cholesterol content (and higher buoyant density), and less Gag precursor polyprotein (Pr65^gag) is associated with detergent-resistant membranes in infected cells. The mechanism by which gPr80^gag facilitates virus release is under investigation. The N-terminal 88 amino acids of gPr80^gag are sufficient to enhance virus release, indicating that the Gag sequences on this protein are not required. Cellular La protein is involved in gPr80^gag function, since over-expression of La phenocopies gPr80^gag in facilitating virus release, and knockdown of La abrogates gPr80^gag-enhancement of virus release. MuLV glyco-gag can also facilitate release of HIV-1 particles from transfected cells, which suggests that these two viruses may share mechanisms for directing virus release through lipid rafts. gPr80^gagalso counteracts the murine APOBEC3 restriction factor (mA3) since gPr80^gagmutant virus shows a defect for establishment of infection in wild-type mice, but not in mA3 knockout animals.