Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
INTERACTION OF HIV WITH ITS CELLULAR RECEPTOR, CD4: PROSPECTS FOR IMMUNOLOGIC INTERVENTION
AIDS Vaccine Research and Clinical Trials. Putney SD and Bolognesi DP, eds. New York, Marcel Dekker, p. 63-92, 1990.. Unique Identifier : AIDSLINE ICDB/91676942 Orloff GM; McDougal JS; Center for Infectious Diseases, Centers for Disease Control,; Atlanta, GA
Abstract:
Because the initial interaction between HIV and host cells involves binding of the viral outer envelope glycoprotein gp120 to the CD4 molecule, much attention has been focused on the envelope and its binding site. Definition of the molecular nature of the CD4 receptor-HIV envelope interaction is not only a key to understanding virus tropism, but, along with other functional domains of HIV proteins, will be required to understand mechanisms of immune interference or escape. The CD4 receptor-HIV interaction is reviewed, including the characteristics of the CD4 molecule, CD4 as a receptor for HIV; location and conformational requirements of the CD4-binding site of the HIV outer envelope gp120, relevance of anti-gp120 antibodies (clues from natural history studies); antibody idiotopes as molecular mimics of HIV gp120; and prospects for a ligand or immunogen eliciting an antibody that blocks the CD4-gp120 interaction. The CD4 molecule specifically binds the HIV envelope glycoprotein gp120 with characteristics of a receptor-ligand interaction; binding has measurable affinity, is saturable, and is inhibited specifically and reversibly. CD4 expression is both sufficient and necessary for binding and infectivity of HIV in human cells. Virtually all the affinity of binding is provided by the gp120-CD4 interaction, as shown by the fact that purified CD4 completely inhibits binding to CD4 cells. If another viral or cellular protein is involved, it must be of exceedingly low affinity or require prior CD4-gp120 binding. With respect to antibody, the measurement of HIV-specific responses has been relatively straightforward, and most HIV-infected individuals mount and sustain a vigorous humoral response. Detection of antibody has become a clinically useful marker for past exposure and probably current infection. Distinguishing whether these responses are clinically important, effective in controlling infection, or potentially protective has been difficult. Serum and cells from HIV-infected people have substantial antiviral effects in vitro that have yet to be reproduced by artificial immunization. Regardless of whether the precise CD4-binding site of gp120 is immunogenic or accessible to antibody, further research on the structure of this site may define immunogens that elicit protective anti-HIV responses, perhaps exceeding those seen in natural infection. (101 Refs)
Keywords: Animal Antigens, CD4/*IMMUNOLOGY CD4-Positive T-Lymphocytes/IMMUNOLOGY Human HIV/*IMMUNOLOGY HIV Antibodies/BIOSYNTHESIS HIV Antigens/*IMMUNOLOGY HIV Envelope Protein gp120/IMMUNOLOGY HIV Infections/*IMMUNOLOGY Prognosis Viral Vaccines/*IMMUNOLOGY MONOGRAPH REVIEW 912130
M91C4099
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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.
