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

• 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

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Infektionsmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Infectious Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

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

late stage

disease

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)