Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Cryptic neutralizing epitopes on SIVagm gp120; role in viral entry.
Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 12. Unique Identifier : AIDSLINE PRIM10/93200961 Allan JS; Whitehead E; Strout K; Dunham R; Kanda P; Department of Virology and Immunology, Southwest Foundation for; Biomedical Research, San Antonio, Texas 78228.
Abstract:
We previously showed that addition of soluble CD4 to SIVagm viruses leads to the enhanced kinetics of infection and cytopathology in human cell lines. We have termed this process receptor-mediated activation. Recent evidence also suggests that HIV-1 and HIV-2 also undergo conformational changes associated with receptor-binding. Although shedding of gp120 following binding to sCD4 has been shown for HIV-1, it is unlikely that this observation relates to important events in viral entry. For SIVagm the activation process also leads to the exposure of neutralizing domains which are highly immunodominant and conserved among SIV and HIV-2 viruses. During primary infection with SIVagm, these novel neutralizing antibodies are the first antibodies detected and their titers remain high throughout the infectious process. In order to define these cryptic epitopes we used two approaches. First, we generated monoclonal antibodies which neutralize sCD4 enhancement of SIVagm and secondly we generated synthetic peptides to selected conserved epitopes of SIVagm and produced antisera for analysis. We have thus far identified one monoclonal antibody that was able to neutralize SIVagm in the presence of sCD4. This antibody (AG1.0) was found to map to gp120 and greater binding occurred when radiolabeled virus was first incubated with sCD4 prior to immunoprecipitation. Additionally, this antibody mapped to the V3-like region of SIVagm. Similarly, antibodies to a synthetic peptide representing the V3-like domain of SIVmac could also neutralize SIVagm/sCD4 infection. These results indicate; 1. the process of viral entry for both SIV and HIV may incorporate similar if not identical steps, 2. the V3-like domain not only acts as a neutralizing domain for these viruses but may also be involved in secondary fusogenic events and 3. the nature of conservation in the V3-like region among SIV viruses is likely due to a lack of immune driven variation as a consequence of its cryptic conformation. Furthermore, the V3-like region of SIVagm may represent part of a larger conformational epitope that undergoes rapid changes during receptor-binding leading to viral fusion.
Keywords: Antibodies, Monoclonal/*IMMUNOLOGY Antigens, CD4/*PHYSIOLOGY Cell Line Epitopes/*ANALYSIS Human HIV Envelope Protein gp120/IMMUNOLOGY/*PHYSIOLOGY HIV-2/PHYSIOLOGY Neutralization Tests SIV/IMMUNOLOGY/*PHYSIOLOGY ABSTRACT 930630
M9361059
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Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
