Effects of HIV type 1 envelope glycoprotein proteolytic processing on antigenicity.
Passaged simian-human immunodeficiency virus (SHIV)-HXBc2P 3.2 exhibits resistance to neutralization by most antibodies and soluble CD4 compared with the parental SHIV-HXBc2; these SHIVs are neutralized equivalently by 2G12 antibody. 2G12 antibody bound proteolytically processed, cell surface envelope glycoproteins from these viruses equivalently; by contrast, other antibodies bound less efficiently to HXBc2P 3.2 envelope glycoproteins than to HXBc2 envelope glycoproteins. We have examined the influence of proteolytic processing of the envelope glycoprotein precursor on antigenicity, comparing antibody binding to cleaved and uncleaved cell surface envelope glycoproteins and to uncleaved soluble trimeric envelope glycoproteins. All envelope glycoproteins bound neutralizing antibodies better than nonneutralizing antibodies, suggesting that their general topology is similar. Differences between cleaved HXBc2 and HXBc2P 3.2 envelope glycoproteins in binding a given antibody, which correlated with susceptibility to neutralization, were not evident in uncleaved envelope glycoproteins. These results indicate that proteolytic processing allows subtle but biologically important adjustments in the conformation of HIV-1 envelope glycoproteins.
Si
Zhihai
Z
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, and Division of AIDS, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Phan
Ngoc
N
Kiprilov
Enko
E
Sodroski
Joseph
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry*; D006801:Humans; D009500:Neutralization Tests; D010447:Peptide Hydrolases / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D014759:Viral Envelope Proteins; D010447:Peptide Hydrolases