Cell fusion activity of the simian immunodeficiency virus envelope protein is modulated by the intracytoplasmic domain.
The processing and biological activity of envelope glycoproteins of pathogenic and nonpathogenic simian immunodeficiency viruses (SIVs) was compared using recombinant vaccinia viruses (rVVs). The env glycoprotein of the nonpathogenic SIVmac1A11 virus caused much larger and more numerous syncytia than the glycoprotein of the pathogenic SIVmac239 virus in several CD4+ human cell lines. The env gene of SIVmac239 codes for a full-length transmembrane (TM) protein, while the SIVmac1A11 virus has a TM protein with a markedly truncated cytoplasmic domain. To determine if TM protein truncation alone might affect the biological properties of viral glycoproteins, we constructed a rVV which expresses a SIVmac239 env with a site-specific mutation yielding a truncated TM protein. This truncated env protein induced extensive fusion of rVV-infected HeLa T4 cell monolayers, whereas no fusion was observed for the parental SIVmac239 env recombinant. The truncated glycoprotein also caused larger and more numerous syncytia than the wild-type SIVmac239 glycoprotein in the human cell lines HUT 78 and CEM x 174. The mutation altered env glycoprotein transport, but did not significantly affect cell surface expression levels or the amount of secreted soluble SU protein. In coinfection assays, the full-length SIVmac239 env protein was found to interfere with fusion induced by the truncated envelope protein. The results thus demonstrate that changes in the cytoplasmic domain of the SIVmac envelope protein can markedly affect the ability to induce cell fusion, an activity of the external domains of the TM-SU glycoprotein complex.
Ritter
G D
GD
Department of Microbiology, University of Alabama at Birmingham 35294-0005.
Mulligan
M J
MJ
Lydy
S L
SL
Compans
R W
RW
D000818:Animals; D001692:Biological Transport; D002459:Cell Fusion; D002460:Cell Line; D005434:Flow Cytometry; D015752:Genes, env; D015757:Genes, rev; D015756:Genes, tat; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000378:metabolism*
D006023:Glycoproteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins