Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease
- PMID: 10358771
- DOI: 10.1146/annurev.immunol.17.1.657
Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease
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.
Similar articles
-
Roles of chemokines and chemokine receptors in HIV-1 infection.Int J Hematol. 2000 Dec;72(4):412-7. Int J Hematol. 2000. PMID: 11197206 Review.
-
Primary SIVsm isolates use the CCR5 coreceptor from sooty mangabeys naturally infected in west Africa: a comparison of coreceptor usage of primary SIVsm, HIV-2, and SIVmac.Virology. 1998 Jun 20;246(1):113-24. doi: 10.1006/viro.1998.9174. Virology. 1998. PMID: 9656999
-
Dendritic cells express multiple chemokine receptors used as coreceptors for HIV entry.J Immunol. 1998 Apr 15;160(8):3933-41. J Immunol. 1998. PMID: 9558100
-
Chemokine (C-C motif) receptor 5-using envelopes predominate in dual/mixed-tropic HIV from the plasma of drug-naive individuals.AIDS. 2008 Jul 31;22(12):1425-31. doi: 10.1097/QAD.0b013e32830184ba. AIDS. 2008. PMID: 18614865
-
Chemokines and chemokine receptors in HIV infection: role in pathogenesis and therapeutics.J Postgrad Med. 2006 Jul-Sep;52(3):210-7. J Postgrad Med. 2006. PMID: 16855325 Review.
Cited by
-
Characterization of a CXCR4 antagonist TIQ-15 with dual tropic HIV entry inhibition properties.PLoS Pathog. 2024 Aug 15;20(8):e1012448. doi: 10.1371/journal.ppat.1012448. eCollection 2024 Aug. PLoS Pathog. 2024. PMID: 39146384 Free PMC article.
-
Development of Anti-HIV Therapeutics: From Conventional Drug Discovery to Cutting-Edge Technology.Pharmaceuticals (Basel). 2024 Jul 4;17(7):887. doi: 10.3390/ph17070887. Pharmaceuticals (Basel). 2024. PMID: 39065738 Free PMC article. Review.
-
Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop.Rev Inst Med Trop Sao Paulo. 2024 Jul 8;66:e38. doi: 10.1590/S1678-9946202466038. eCollection 2024. Rev Inst Med Trop Sao Paulo. 2024. PMID: 39052025 Free PMC article.
-
The complex nature of CXCR4 mutations in WHIM syndrome.Front Immunol. 2024 Jul 5;15:1406532. doi: 10.3389/fimmu.2024.1406532. eCollection 2024. Front Immunol. 2024. PMID: 39035006 Free PMC article. Review.
-
Defining the Effects of PKC Modulator HIV Latency-Reversing Agents on Natural Killer Cells.Pathog Immun. 2024 Apr 24;9(1):108-137. doi: 10.20411/pai.v9i1.673. eCollection 2024. Pathog Immun. 2024. PMID: 38765786 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials