Virions of primary human immunodeficiency virus type 1 isolates resistant to soluble CD4 (sCD4) neutralization differ in sCD4 binding and glycoprotein gp120 retention from sCD4-sensitive isolates.
Primary isolates of human immunodeficiency virus type 1 (HIV-1) are much less sensitive to neutralization by soluble CD4 (sCD4) and sCD4-immunoglobulin (Ig) chimeras (CD4-IgG) than are HIV-1 strains adapted to growth in cell culture. We demonstrated that there are significant reductions (10- to 30-fold) in the binding of sCD4 and CD4-IgG to intact virions of five primary isolates compared with sCD4-sensitive, cell culture-adapted isolates RF and IIIB. However, soluble envelope glycoproteins (gp120) derived from the primary isolate virions, directly by detergent solubilization or indirectly by recombinant DNA technology, differed in affinity from RF and IIIB gp120 by only one- to threefold. The reduced binding of sCD4 to these primary isolate virions must therefore be a consequence of the tertiary or quaternary structure of the envelope glycoproteins in their native, oligomeric form on the viral surface. In addition, the rate and extent of sCD4-induced gp120 shedding from these primary isolates was lower than that from RF. We suggest that reduced sCD4 binding and increased gp120 retention together account for the relative resistance of these primary isolates to neutralization by sCD4 and CD4-IgG and that virions of different HIV-1 isolates vary both in the mechanism of sCD4 binding and in subsequent conformational changes in their envelope glycoproteins.
Moore
J P
JP
Chester Beatty Laboratories, Institute of Cancer Research, London, United Kingdom.
McKeating
J A
JA
Huang
Y X
YX
Ashkenazi
A
A
Ho
D D
DD
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D002461:Cell Line, Transformed; D003902:Detergents; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D012995:Solubility; D013045:Species Specificity; D013696:Temperature; D014771:Virion / Q000276:immunology / Q000378:metabolism*; D014776:Virus Cultivation
D015704:CD4 Antigens; D003902:Detergents; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G