Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4.
Human immunodeficiency virus type 1 (HIV-1) infects human CD4+ cells by a high-affinity interaction between its envelope glycoprotein gp120 and the CD4 molecule on the cell surface. Subsequent virus entry into the cells involves other steps, one of which could be cleavage of the gp120 followed by virus-cell fusion. The envelope gp120 is highly variable among different HIV-1 isolates, but conserved amino acid sequence motifs that contain potential proteolytic cleavage sites can be found. Following incubation with a soluble form of CD4, we demonstrate that gp120 of highly purified HIV-1 preparations is, without addition of exogenous proteinase, cleaved most likely in the V3 loop, yielding two proteins of 50 and 70 kDa. The extent of gp120 proteolysis is HIV-1 strain dependent and correlates with the recombinant soluble CD4 sensitivity to neutralization of the particular strain. The origin of the proteolytic activity in the virus preparations remains unclear. The results support the hypothesis that cleavage of gp120 is required for HIV infection of cells.
Werner
A
A
Department of Medicine, School of Medicine, University of California, San Francisco 94143-0128.
Levy
J A
JA
D000163:Acquired Immunodeficiency Syndrome / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015704:CD4 Antigens / Q000378:metabolism*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D010450:Endopeptidases