Resistance of primary isolates of human immunodeficiency virus type 1 to neutralization by soluble CD4 is not due to lower affinity with the viral envelope glycoprotein gp120.

Abstract

August 16, 1991) ABSTRACT Recombinant soluble CD4 (rsCD4) has potent antiviral activity against cell line-adapted isolates of the human immunodeficiency virus type 1 (iHV-1) but low activity toward H1V-1 primary isolates from patients. A simple hypothesis proposed to explain this discrepancy, which questions the therapeutic utility of soluble CD4-based approaches, is that the major envelope glycoprotein, gpl20, of patient virus has lower

Biological consequences of human immunodeficiency virus type 1 envelope polymorphism: does variation matter?: 1995 Fleming Lecture Delivered at the 134th Meeting of the Society for General Microbiology, 26 March 1996

“…However, this conclusion was based on the failure to demonstrate differences in the affinities of monomeric gp120 proteins from primary and laboratory cultured viruses for sCD4 (Turner et al,, 1992). Our results suggest that such conclusions may be misleading, since monomeric gp120 proteins derived from single primary virus isolates display a wide range of relative binding affinities for CD4, such that the overall population may demonstrate a reduced net affinity.…”

“…Several reports considering the resistance of primary viruses to neutralization by sCD4 have proposed that this is due to a reduced affinity of the envelope for CD4, apparent in the oligomeric form of the glycoprotein, but not in the monomer (Ashkenazi et al, 1991;Turner et al, 1992). However, this conclusion was based on the failure to demonstrate differences in the affinities of monomeric gp120 proteins from primary and laboratory cultured viruses for sCD4 (Turner et al,, 1992).…”

“…Primary viruses are generally insensitive to neutralization by sCD4 and antibodies which are capable of neutralizing laboratory adapted virus isolates (Ashkenazi eta ;Turner et al, 1992;Wrin eta]., 1995). Understanding the mechanism(s) of this resistance is of great importance, both in terms of developing effective immunotherapies and in vaccine design.…”

“…relating to primary virus glycoprotein function have studied single proteins, with the implicit assumption that a single clone would be representative of the virus population (Ashkenazi et al, 1991;Daar & Ho, 1991;Turner et al, 1992). In order to address the characteristics of primary virus populations and their interactions with CD4 and neutralizing antibodies, we have studied multiple gpI20 glycoproteins derived from several primary isolates.…”

Rapid Prescreening for Antiviral Agents against HIV-1 Based on Their Inhibitory Activity in Site-Directed Immunoassays. Approaches Applicable to Epidemic HIV-1 Strains

“…The observation that many primary HIV-1 isolates are resistant to the antiviral effect of soluble CD4, the cell receptor for HIV-1, unlike laboratory strains of the virus (Ashkenazi et al, 1991;Brighty et al, 1991;Moore et a/., 1992;Turner et al, 1992) suggests the importance of including primary HIV-1 isolates belonging to distinct HIV-1 families (Sternberg, 1992) into any investigation concerning antiviral compounds before considering their application for antiviral chemotherapy and designing clinical trials. Such caution is further justified by the observation that several compounds having antiviral activity against HIV-1 IIIB (Neurath et a/., 1991) were inactive against HIV-1 MN (fable 1).…”