Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease.

Annu Rev Immunol. 1999;17:657-700. Unique Identifier : AIDSLINE MED/99286823
Berger EA; Murphy PM; Farber JM; Laboratory of Viral Diseases, National Institute of Allergy and; Infectious Diseases, National Institutes of Health, Bethesda,; Maryland 20892, USA. Edward_Berger@nih.gov

Abstract: In addition to CD4, the human immunodeficiency virus (HIV) requires a coreceptor for entry into target cells. The chemokine receptors CXCR4 and CCR5, members of the G protein-coupled receptor superfamily, have been identified as the principal coreceptors for T cell line-tropic and macrophage-tropic HIV-1 isolates, respectively. The updated coreceptor repertoire includes numerous members, mostly chemokine receptors and related orphans. These discoveries provide a new framework for understanding critical features of the basic biology of HIV-1, including the selective tropism of individual viral variants for different CD4+ target cells and the membrane fusion mechanism governing virus entry. The coreceptors also provide molecular perspectives on central puzzles of HIV-1 disease, including the selective transmission of macrophage-tropic variants, the appearance of T cell line-tropic variants in many infected persons during progression to AIDS, and differing susceptibilities of individuals to infection and disease progression. Genetic findings have yielded major insights into the in vivo roles of individual coreceptors and their ligands; of particular importance is the discovery of an inactivating mutation in the CCR5 gene which, in homozygous form, confers strong resistance to HIV-1 infection. Beyond providing new perspectives on fundamental aspects of HIV-1 transmission and pathogenesis, the coreceptors suggest new avenues for developing novel therapeutic and preventative strategies to combat the AIDS epidemic.

Keywords: JOURNAL ARTICLE REVIEW REVIEW, ACADEMIC Alleles Human HIV Infections/*ETIOLOGY/TRANSMISSION HIV-1/GENETICS/ISOLATION & PURIF/*PATHOGENICITY Membrane Fusion Models, Biological Polymorphism (Genetics) Receptors, Chemokine/GENETICS/*PHYSIOLOGY Receptors, CCR5/PHYSIOLOGY Receptors, CXCR4/PHYSIOLOGY Receptors, HIV/GENETICS/*PHYSIOLOGY Virulence
991130
A99B1093

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1999. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .