ANALYSIS OF THE CELL-FUSION ACTIVITIES OF CHIMERIC SIMIAN IMMUNODEFICIENCY VIRUS MURINE LEUKEMIA-VIRUS ENVELOPE PROTEINS - INHIBITORY EFFECTS OF THE R-PEPTIDE

It was previously reported that truncation or proteolytic removal of t he C-terminal 16 amino acids (the R peptide) from the cytoplasmic tail of the murine leukemia virus (MuLV) envelope protein greatly increase s its fusion activity, In this study, to investigate the specificity o f the effect of the R peptide on the fusion activity of viral envelope proteins, we expressed simian immunodeficiency virus (SN)-MuLV chimer ic proteins in which the entire cytoplasmic tail of the SIV envelope p rotein was replaced by either the full-length MuLV cytoplasmic tail or a truncated MuLV cytoplasmic tail with the R peptide deleted. Extensi ve fusion of CD4-positive cells with the chimeric protein containing a truncated MuLV cytoplasmic tail was observed. In contrast, no cell fu sion activity was found for the chimeric protein,vith a full-length Mu LV cytoplasmic tail. We constructed another SIV-MuLV chimeric protein in which the MuLV R peptide was added to an SIV envelope protein cytop lasmic tail 17 amino acids from its membrane-spanning domain. No fusio n activity was observed within this construct, while the corresponding truncated SIV envelope protein lacking the R peptide showed extensive fusion activity, No significant difference in the transport or surfac e expression was observed among the various SIV-MuLV chimeric proteins and the truncated SN envelope protein. Our results thus demonstrate t hat the MuLV R peptide has profound inhibitory effects on virus-induce d cell fusion, not only with MuLV but also in a distantly related retr oviral envelope protein which utilizes a different receptor and fuses different cell types.