Plasma factors in human blood alter the entry and neutralization properties of HIV-1: implications for gp120-based vaccine approaches.
Int Conf AIDS 1996 Jul 7-12; 11:8 (abstract no. Mo.A.270) Nara PL, Merges M, Wu SC, Spouge J; Virus Biology Section, LTCB, DBS, NCI-FCRDC, Frederick, MD. Fax: 301-846-6194.
Conventional virology suggests one important aspect of viral tropism/pathogenicity is mediated by specific virus ligands interacting with specific cellular receptors. Factors, however, which govern and/or influence the specificity of these interactions within the host may involve colloidal or soluble molecules capable of additional enzymatic or cooperative interactions. We have reanalyzed the immunobiology of field isolates and laboratory strains under more relevant physiologic and/or cellular conditions in an effort to determine if other factors exist which could provide new insights into HIV-1 entry than might be currently appreciated. Primary cultures of either peripheral blood mononuclear cells (PBMC's) or blood-derived macrophages (BDM) in the presence of physiologic concentrations of normal human blood plasma were found to enhance the infectivity of primary isolates by recruiting otherwise non-infectious particles in a first order and time dependent way. This enhancement was Ca++ dependent, heat labile in PBMC, heat stable in MDM and not present in chimpanzee plasma. Neutralization and blocking studies will be presented demonstrating the recruited infectious fraction exhibits significant resistance to neutralization by antibodies, soluble CD4, and env-acting anti-viral compounds. Further immunochemical evidence for these plasma-mediated alterations to the gp120/41 include changes in immunoreactivity, stable cleavage of the viral envelope gp120, and appear to require that virus/cell/plasma react together. These cumulative results suggest that cell-free HIV-1 in physiologic concentrations of CPDA-1-collected normal human plasma result in significant alterations of the virus infectivity, cellular entry kinetics, and immunochemical properties. When applied to our current and ongoing vaccine efforts, immunogens considering the viral envelope gp 120/41 may need to reconsider these additional extracellular modifications and/or molecular interactions occurring to the glycoprotein in the plasma compartment.
Keywords: AEGIS, HIV-1, Plasma, Antigens, CD4, Vaccines, Macrophages, SK&F 106528, Human, blood, virology, ICA11
