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PMID: 8474162 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4.

Journal of virology ·Vol. 67 ·No. 5 ·1993-05-00 ·Pages 2566-74

Werner A, Levy JA

Abstract

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.

MeSH Terms
Acquired Immunodeficiency Syndrome/metabolism Antibodies, Monoclonal Antibodies, Viral CD4 Antigens/metabolism Cells, Cultured Endopeptidases/drug effects,metabolism HIV Envelope Protein gp120/immunology,metabolism HIV-1/isolation & purification,metabolism Humans Leukocytes, Mononuclear/microbiology Neutralization Tests Peptide Fragments/metabolism Protease Inhibitors/pharmacology Recombinant Proteins/metabolism Solubility Species Specificity
Chemicals
Antibodies, Monoclonal Antibodies, Viral CD4 Antigens HIV Envelope Protein gp120 Peptide Fragments Protease Inhibitors Recombinant Proteins Endopeptidases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Werner A
Department of Medicine, School of Medicine, University of California, San Francisco 94143-0128.
Levy J A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.5.2566-2574.1993
Published
1993-05-00
Pages
2566-74
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237577
Subset
IM
Grants
NIAID NIH HHS · R0I AI 29394 · United States
PHS HHS · UOI A1 26471 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.5.2566-2574.1993 PMC Full Text View journal details
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