Journal ArticleDOI
CHEMOKINE RECEPTORS AS HIV-1 CORECEPTORS: Roles in Viral Entry, Tropism, and Disease
TLDR
In this paper, 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 macrophagetropic HIV-1 isolates, respectively.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 C 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.read more
Citations
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Journal Article
International Union of Pharmacology. XXII. Nomenclature for Chemokine Receptors
Philip M. Murphy,Marco Baggiolini,Israel F. Charo,Caroline A. Hébert,Richard Horuk,Kouji Matsushima,Louis H. Miller,Joost J. Oppenheim,Christine A. Power +8 more
TL;DR: A widely accepted receptor nomenclature system is described, ratified by the International Union of Pharmacology, that is facilitating clear communication in this area and updating current concepts of the biology and pharmacology of the chemokine system.
Journal ArticleDOI
T-cell function and migration. Two sides of the same coin.
TL;DR: This review will concentrate on the migration of T cells, which are at the heart of most adaptive immune responses, since T cells respond to pathogens only on direct contact with pathogen-derived antigen.
Journal ArticleDOI
Chemokines and disease.
Craig Gerard,Barrett J. Rollins +1 more
TL;DR: Several diseases that are associated with inappropriate activation of the chemokine network are examined, including cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease.
Journal ArticleDOI
Mechanisms of viral membrane fusion and its inhibition
Debra M. Eckert,Peter S. Kim +1 more
TL;DR: The fusion mechanism involves a transient conformational species that can be targeted by therapeutic strategies and is likely utilized by a wide variety of enveloped viruses for which similar therapeutic interventions should be possible.
Journal ArticleDOI
The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus
Elisa Scarselli,Helenia Ansuini,Raffaele Cerino,Rosa Maria Roccasecca,Stefano Acali,Gessica Filocamo,Cinzia Traboni,Alfredo Nicosia,Riccardo Cortese,Alessandra Vitelli +9 more
TL;DR: It is discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81, and the receptor responsible for E2 binding to human hepatic cells is identified as the human scavenger receptor class B type I (SR‐BI).
References
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Journal ArticleDOI
HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein-Coupled Receptor
TL;DR: A cofactor for HIV-1 (human immunodeficiency virus-type 1) fusion and entry was identified with the use of a novel functional complementary DNA (cDNA) cloning strategy that is a putative G protein-coupled receptor with seven transmembrane segments.
Journal Article
HIV-1 Entry Cofactor: Functional cDNA Cloning of a Seven-Transmembrane, G Protein–Coupled Receptor
TL;DR: Fusin this article is a putative G protein-coupled receptor with seven transmembrane segments, which enabled CD4-expressing nonhuman cell types to support HIV-1 Env-mediated cell fusion and infection.
Journal ArticleDOI
Identification of a major co-receptor for primary isolates of HIV-1
Hongkui Deng,Rong Liu,Wilfried Ellmeier,S Choe,Derya Unutmaz,M Burkhart,P Di Marzio,Shoshana Marmon,R E Sutton,C M Hill,C B Davis,S C Peiper,T J Schall,Dan R. Littman,Nathaniel R. Landau +14 more
TL;DR: The principal cofactor for entry mediated by the envelope glycoproteins of primary macrophage-tropic strains of HIV-1 is CC-CKR-5, a receptor for the β-chemokines RANTES, Mip-1α and MIP-1β.
Journal ArticleDOI
HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5.
Tatjana Dragic,Virginia M. Litwin,Graham P. Allaway,Scott R. Martin,Yaoxing Huang,Kirsten A. Nagashima,Charmagne Cayanan,Paul J. Maddon,Richard A. Koup,John P. Moore,William A. Paxton +10 more
TL;DR: The β-chemokine receptor CC-CKR-5 as mentioned in this paper is a second receptor for NSI primary viruses, which allows env-mediated cell-cell membrane fusion, but it does not allow the fusion of cells from some HIV-1-exposed uninfected individuals.
Journal ArticleDOI
Homozygous Defect in HIV-1 Coreceptor Accounts for Resistance of Some Multiply-Exposed Individuals to HIV-1 Infection
Rong Liu,William A. Paxton,Sunny Choe,Daniel Ceradini,Scott R. Martin,Richard Horuk,Marcy E. MacDonald,Heidi Stuhlmann,Richard A. Koup,Nathaniel R. Landau +9 more
TL;DR: A CKR-5 allele present in the human population appears to protect homozygous individuals from sexual transmission of HIV-1 and is suggested to provide a means of preventing or slowing disease progression.
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