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Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load

Artikel i vetenskaplig tidskrift
Författare U. Karlsson
L. Antonsson
B. Ljungberg
P. Medstrand
J. Esbjornsson
M. Jansson
Magnus Gisslén
Publicerad i Aids
Volym 26
Nummer/häfte 14
Sidor 1739-1744
ISSN 0269-9370
Publiceringsår 2012
Publicerad vid Institutionen för biomedicin, avdelningen för infektionssjukdomar
Sidor 1739-1744
Språk en
Länkar ttp://dx.doi.org/10.1097/QAD.0b013e...
Ämnesord CCR3, cerebrospinal fluid viral load, CXCR6, HIV-1 R5, late stage disease, subtype C, immunodeficiency-virus type-1, central-nervous-system, coreceptor usage, antiretroviral therapy, chemokine receptors, infection, plasma, ccr5, brain, microglia, ice rw, 1988, science, v239, p586
Ämneskategorier Immunologi inom det medicinska området, Infektionsmedicin

Sammanfattning

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

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