BACKGROUND: Chemokine receptors serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine central nervous system infection pathogenesis. Using an in vitro functional entry assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid (CSF) and plasma in 46 subjects. METHODS: Paired CSF and plasma samples were selected from subjects with a range of CD4 T cell counts. Amplified populations of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for viral tropism and phylogeny. RESULTS: CSF and plasma pairs were mainly concordant for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma. Although R5+X4 tropism was associated with advanced immunodeficiency, all 4 subjects with acquired immunodeficiency syndrome dementia complex had R5 tropism in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and X4 viruses and viruses able to utilize either coreceptor, suggesting both virus exchange between compartments and autonomous CSF virus evolution. CONCLUSIONS: Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize CXCR4 are also present. Discordant tropism in CSF and plasma may have implications for R5 inhibitor therapy.
BACKGROUND: Chemokine receptors serve as coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, influence cell tropism, and may critically determine central nervous system infection pathogenesis. Using an in vitro functional entry assay, we examined utilization of 2 principal coreceptors in cerebrospinal fluid (CSF) and plasma in 46 subjects. METHODS: Paired CSF and plasma samples were selected from subjects with a range of CD4 T cell counts. Amplified populations of env sequences were characterized as using CCR5 (R5), CXCR4 (X4), or both receptors (R5+X4). Individual clones derived from 3 subjects were analyzed for viral tropism and phylogeny. RESULTS: CSF and plasma pairs were mainly concordant for R5 (36/46) or R5+X4 (5/46) viruses. However, 5 pairs were discordant, 2 of which had the R5+X4 phenotype in CSF despite having the R5 phenotype in plasma. Although R5+X4 tropism was associated with advanced immunodeficiency, all 4 subjects with acquired immunodeficiency syndrome dementia complex had R5 tropism in CSF. Clones derived from R5+X4-tropic populations revealed mixtures of R5 and X4 viruses and viruses able to utilize either coreceptor, suggesting both virus exchange between compartments and autonomous CSF virus evolution. CONCLUSIONS: Although R5 viruses predominate in the CSF, HIV-1 populations able to utilize CXCR4 are also present. Discordant tropism in CSF and plasma may have implications for R5 inhibitor therapy.
Authors: Jose A Muñoz-Moreno; Carmina R Fumaz; Anna Prats; Maria J Ferrer; Eugènia Negredo; Núria Pérez-Alvarez; José Moltó; Guadalupe Gómez; Maite Garolera; Bonaventura Clotet Journal: J Neurovirol Date: 2010-05 Impact factor: 2.643
Authors: Katlego Sojane; Richard T Kangethe; Christina C Chang; Mahomed-Yunus S Moosa; Sharon R Lewin; Martyn A French; Thumbi Ndung'u Journal: AIDS Res Hum Retroviruses Date: 2018-05-23 Impact factor: 2.205
Authors: Rebecca L Dunfee; Elaine R Thomas; Paul R Gorry; Jianbin Wang; Joann Taylor; Kevin Kunstman; Steven M Wolinsky; Dana Gabuzda Journal: Proc Natl Acad Sci U S A Date: 2006-10-02 Impact factor: 11.205
Authors: S G Parisi; C Andreoni; L Sarmati; C Boldrin; A R Buonomini; S Andreis; R Scaggiante; M Cruciani; O Bosco; V Manfrin; G d'Ettorre; C Mengoli; V Vullo; G Palù; M Andreoni Journal: J Clin Microbiol Date: 2011-03-02 Impact factor: 5.948
Authors: Guillaume Martin-Blondel; David Brassat; Jan Bauer; Hans Lassmann; Roland S Liblau Journal: Nat Rev Neurol Date: 2016-01-18 Impact factor: 42.937
Authors: Ulf Karlsson; Liselotte Antonsson; Johanna Repits; Patrik Medstrand; Christer Owman; Karin Kidd-Ljunggren; Lars Hagberg; Bo Svennerholm; Marianne Jansson; Magnus Gisslén; Bengt Ljungberg Journal: AIDS Res Hum Retroviruses Date: 2009-12 Impact factor: 2.205