Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
Receptor binding mediates activation of fusogenic events in viral penetration.
Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:26 (abstract no. 10). Unique Identifier : AIDSLINE PRIM8/900010 Allan JS; Short M; Bradford D; Whitehead E; Department of Virology and Immunology, Southwest Foundation for; Biomedical Research, San Antonio, Texas
Abstract:
Recent studies have suggested that events involved in viral entry are initiated by receptor binding to the viral membrane. Based on our previous studies we proposed that CD4, either as soluble form or as a cell membrane constituent, activates the viral membrane by inducing conformational changes leading to viral fusion. In the case of SIVagm(tyo) and SIVagm(gri-1), considerable enhancement of infection was observed when sCD4 was incubated with the virus. As much as a 100 fold increase in infectivity of SIVagm was found correlating with conformational changes within the envelope. Indirect evidence points to a highly conserved and immunodominant epitope(s) on envelope proteins that is exposed upon CD4 binding to gp120. Naturally infected African green monkeys and experimentally infected rhesus macaques invariably generate such antibodies which can block sCD4 activation. These antibodies are the first antibodies observed following infection and the titers rise rapidly over time and are persistent. Rabbits immunized with SIVagm also generate these inhibitory antibodies which are primary antibody responses. Additionally, we have found that determinants on CD4 sufficient for activation of SIVagm appear to reside on the N-terminal V1 loop based on the ability of peptides and expressed proteins to affect SIVagm enhancement. To study the possibility that receptor-mediated viral activation is a common transitional state for primate immunodeficiency viruses, we have identified both HIV-1 and SIVmac variants by cell culture passage in the presence of sCD4. These variants were found to infect and replicate as efficiently as non-treated viral preparations and could be blocked with anti-CD4 monoclonal antibodies which also blocked SIVagm(tyo-1) activation by sCD4. These results suggest that CD4 activation may be a normal process in the events leading to viral entry and replication and further suggest that this activation can be exploited for new vaccine and therapeutic strategies.
Keywords: Animal Antibodies, Monoclonal/IMMUNOLOGY Antibodies, Viral/BIOSYNTHESIS Antigens, CD4/*IMMUNOLOGY Cell Membrane/IMMUNOLOGY CD4-Positive T-Lymphocytes/IMMUNOLOGY HIV Envelope Protein gp120/*IMMUNOLOGY HIV-1/GENETICS Lymphocyte Transformation/IMMUNOLOGY Macaca mulatta Protein Conformation Rabbits Receptors, Virus/*IMMUNOLOGY SIV/GROWTH & DEVELOPMENT/GENETICS/*IMMUNOLOGY Variation (Genetics) Viral Vaccines Virus Activation/*IMMUNOLOGY ABSTRACT 910730
M9170984
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
