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.


METHODS
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.


CONCLUSIONS
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.
Department of Clinical Sciences, Lund University, Lund, Sweden. ulf.karlsson@med.lu.se
Ulf
U
Karlsson
Liselotte
L
Antonsson
Bengt
B
Ljungberg
Patrik
P
Medstrand
Joakim
J
Esbjörnsson
Marianne
M
Jansson
Magnus
M
Gisslen
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000163:Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006679:HIV Seropositivity / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D008297:Male; D010641:Phenotype; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D012189:Retrospective Studies; D018523:Tropism / Q000235:genetics; D019562:Viral Load
C106330:CXCR6 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D000075744:Receptors, CXCR6; D019707:Receptors, Chemokine; D015728:Receptors, HIV; D011991:Receptors, Virus