Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load
Författare
Summary, in English
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. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
Avdelning/ar
Publiceringsår
2012
Språk
Engelska
Sidor
1739-1744
Publikation/Tidskrift/Serie
AIDS
Volym
26
Issue
14
Dokumenttyp
Artikel i tidskrift
Förlag
Lippincott Williams & Wilkins
Ämne
- Infectious Medicine
Nyckelord
- CCR3
- cerebrospinal fluid viral load
- CXCR6
- HIV-1 R5
- late stage
- disease
- subtype C
Status
Published
Forskningsgrupp
- Drug Target Discovery
ISBN/ISSN/Övrigt
- ISSN: 1473-5571