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Published on: March 8, 2012
Human immunodeficiency virus type 1 envelope gp120 is cleaved after incubation with recombinant soluble CD4
1Department of Medicine, School of Medicine, University of California, San Francisco 94143-0128.
Insights
Human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 is cleaved in purified virus preparations. This cleavage, occurring without added enzymes, is essential for HIV-1 cell entry and infection.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infects CD4+ cells via gp120-CD4 interaction.
- Virus entry involves multiple steps, potentially including gp120 cleavage and fusion.
- HIV-1 gp120 exhibits high variability but contains conserved motifs with cleavage sites.
Purpose of the Study:
- To investigate gp120 cleavage in purified HIV-1 preparations.
- To determine if gp120 cleavage occurs spontaneously or requires exogenous proteases.
- To correlate gp120 cleavage with HIV-1 infectivity and neutralization sensitivity.
Main Methods:
- Incubation of purified HIV-1 with soluble CD4.
- Analysis of gp120 cleavage products using protein electrophoresis.
- Assessment of HIV-1 strain-dependent proteolysis.
- Correlation with recombinant soluble CD4 neutralization sensitivity.
Main Results:
- gp120 in purified HIV-1 preparations undergoes cleavage upon incubation with soluble CD4.
- Cleavage occurs without added proteases, yielding 50 and 70 kDa fragments, likely in the V3 loop.
- The extent of gp120 proteolysis varies among HIV-1 strains.
- Proteolysis extent correlates with sensitivity to neutralization by soluble CD4.
Conclusions:
- gp120 cleavage is an intrinsic property of purified HIV-1 preparations.
- This cleavage is likely essential for HIV-1 cell entry and infection.
- The source of proteolytic activity within the virus preparations requires further investigation.
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.
