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15 March 2005

Volume 191, Number 6
The Journal of Infectious Diseases 2005;191:890–898
© 2005 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2005/19106-0010$15.00
DOI: 10.1086/428095
MAJOR ARTICLE

HIV‐1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia

Serena S. Spudich,1

Wei Huang,3

Annelie C. Nilsson,1

Christos J. Petropoulos,3

Teri J. Liegler,2

Jeannette M. Whitcomb,3 and

Richard W. Price1

1Department of Neurology, University of California–San Francisco, and 2Gladstone Institute of Virology and Immunology, San Francisco, and 3ViroLogic, South San Francisco, California

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.

Received 15 July 2004; accepted 13 December 2004; electronically published 9 February 2005.

Reprints or correspondence: Dr. Serena S. Spudich, Dept. of Neurology, Rm. 4M62, San Francisco General Hospital, 1001 Potrero Ave., San Francisco, CA 94110‐3518 ().

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Online publication date: 1-Jun-2009.
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James L. Buescher, Fenghai Duan, Junfeng Sun, Richard W. Price, Tsuneya Ikezu. (2009) OTK18 Levels in Plasma and Cerebrospinal Fluid Correlate with Viral Load and CD8 T-cells in Normal and AIDS Patients. Journal of Neuroimmune Pharmacology 3:4, 230-235
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  • Presented in part: 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, 8–11 February 2004 (abstract G‐7).

    Potential conflicts of interest: W.H., C.J.P., and J.M.W. are employees of ViroLogic.

    Financial support: National Institutes of Health (grants R01 NS37660, R01 MH62701, and MO1‐RR‐00083‐36).

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