Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein.
The cytopathic effects of human immunodeficiency virus type 1 (HIV-1) infection are specific for cells that express the CD4 viral receptor and consist of syncytium formation and single-cell lysis. Here we report that a mutation (517A) affecting the amino terminus of the HIV-1 gp41 transmembrane envelope glycoprotein resulted in a virus that was markedly less cytopathic than was wild-type HIV-1. In systems in which cell-to-cell transmission of HIV-1 occurred, the replication ability of the 517A virus was comparable with that of the wild-type virus. Even though the levels of viral protein expression, virion production, and interaction of the envelope glycoproteins with CD4 were similar for the 517A and wild-type viruses, both syncytium formation and single-cell lysis were attenuated for the 517A mutant virus. These results demonstrate that an envelope glycoprotein region important for mediating post-receptor binding events in cell membrane fusion is important for the induction of cytopathic effects by HIV-1. These results also indicate that levels of HIV-1 viral proteins or viral particles produced in infected cells are in themselves not sufficient to induce cytopathic effects.
Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts.
M
M
Kowalski
L
L
Bergeron
T
T
Dorfman
W
W
Haseltine
J
J
Sodroski
D000595:Amino Acid Sequence; D015139:Blotting, Southern; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D015700:HIV Envelope Protein gp41 / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D015183:Restriction Mapping; D013601:T-Lymphocytes; D014771:Virion / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D015700:HIV Envelope Protein gp41; D012194:RNA-Directed DNA Polymerase