HIV-1 chemokine coreceptor utilization in paired cerebrospinal fluid and plasma samples: a survey of subjects with viremia.
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.
Spudich
Serena S
SS
Department of Neurology, University of California-San Francisco, San Francisco, California, USA. sspudich@itsa.ucsf.edu.
Huang
Wei
W
Nilsson
Annelie C
AC
Petropoulos
Christos J
CJ
Liegler
Teri J
TJ
Whitcomb
Jeannette M
JM
Price
Richard W
RW
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000821:virology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001769:Blood / Q000821:virology*; D018791:CD4 Lymphocyte Count; D002555:Cerebrospinal Fluid / Q000821:virology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015686:Gene Products, env / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014766:Viremia / Q000821:virology*
D019380:Anti-HIV Agents; D015686:Gene Products, env; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4