Attenuation of human immunodeficiency virus type 1 cytopathic effect by a mutation affecting the transmembrane envelope glycoprotein

J Virol. 1991 Jan;65(1):281-91. doi: 10.1128/JVI.65.1.281-291.1991.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Blotting, Southern
  • CD4 Antigens / analysis
  • Cell Line
  • Cell Transformation, Viral*
  • Cells, Cultured
  • DNA, Viral / genetics
  • DNA, Viral / isolation & purification
  • HIV Envelope Protein gp41 / genetics*
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity
  • HIV-1 / physiology
  • Humans
  • Kinetics
  • Leukocytes, Mononuclear / physiology
  • Molecular Sequence Data
  • Mutation*
  • Plasmids
  • RNA-Directed DNA Polymerase / metabolism
  • Restriction Mapping
  • T-Lymphocytes
  • Virion / genetics
  • Virion / pathogenicity
  • Virion / physiology
  • Virus Replication*

Substances

  • CD4 Antigens
  • DNA, Viral
  • HIV Envelope Protein gp41
  • RNA-Directed DNA Polymerase