Objective: To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples.
Design: Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS).
Methods: HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4+ T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1).
Results: All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4+ T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4+ T-cell counts. The use of other alternative coreceptors was less pronounced.
Conclusion: Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4+ T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.
aDepartment of Clinical Sciences, Lund University, Lund
bDepartment of Experimental Medical Science, Lund University, Lund
cDepartment of Laboratory Medicine, Lund University, Malmö
dDepartment of Laboratory Medicine, Lund University, Lund
eDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm
fDepartment of Infectious Diseases, University of Gothenburg, Gothenburg, Sweden.
Correspondence to Dr Ulf Karlsson, Department of Infectious Diseases, Lund University Hospital, Skåne University Hospital, Klinikgatan 3, Lund 22185, Sweden. Fax: +46 46 323895; e-mail: email@example.com
Received 2 April, 2012
Revised 8 May, 2012
Accepted 17 May, 2012