Presence of HIV-1 R5 viruses in cerebrospinal fluid even in patients harboring R5X4/X4 viruses in plasma.
BACKGROUND
HIV-1 viruses have the ability to use CCR5 or CXCR4 coreceptors either solely (R5 or X4) or in combination (R5X4). The CCR5 antagonists block HIV entry into the cell and are specifically active against HIV-1 R5 strains. The objectives of this study were to investigate the predicted tropism of viruses present in paired cerebrospinal fluid (CSF) and plasma in a group of 22 HIV-1-infected patients with neurological disorders and to search for eventual discordance of predicted virus tropism between both compartments.


METHODS
Paired CSF and plasma samples were selected from subjects harboring neurological disorders. V3 env was amplified and bulk sequenced, and HIV-1 coreceptor usage was determined from the V3 env region sequence by Geno2Pheno and position-specific scoring matrices (PSSM) algorithms.


RESULTS
The majority of subjects (19 of 22) had concordant virus predicted tropism in both compartments. All patients having R5-tropic viruses in plasma had R5-tropic viruses in CSF (17 of 22). Patients having R5X4/X4-tropic viruses in plasma could have R5X4/X4-using (2 of 22) or R5-tropic viruses (3 of 22) in CSF. The case of R5-tropic viruses in plasma and R5X4/X4-tropic viruses in CSF was never observed.


CONCLUSIONS
The majority of these patients have R5-using viruses in CSF that is mainly concordant with the predicted tropism in plasma. However, R5X4/X4 tropism in plasma does not necessarily mean the same predicted tropism in CSF compartment. Then, clinical therapeutic trials testing the clinical response to the CCR5 antagonists in patients with neurological disorders could be envisaged to analyze the effects of this therapeutic class in this setting.
Soulié
Cathia
C
Université Pierre et Marie Curie-Paris 6, UMR S-943 Paris, F-75013 France. cathia.soulie@psl.aphp.fr
Tubiana
Roland
R
Simon
Anne
A
Lambert-Niclot
Sidonie
S
Malet
Isabelle
I
Canestri
Ana
A
Brunet
Christel
C
Murphy
Robert
R
Katlama
Christine
C
Calvez
Vincent
V
Marcelin
Anne-Geneviève
AG
D015526:AIDS Dementia Complex / Q000097:blood / Q000134:cerebrospinal fluid / Q000821:virology*; D000328:Adult; D000368:Aged; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics; D012367:RNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D055815:Young Adult
C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4