Background:  GB virus C (GBV-C) is an orphan Flavivirus distantly related to hepatitis C virus (HCV). GBV-C infection in humans is common and its transmission is similar to both HCV and HIV, including sexual, parenteral, and vertical transmission. The aim of this study was to investigate the presence and compartmentalization of GBV-C strains in plasma, peripheral blood mononuclear cells (PBMC), and cerebrospinal fluid (CSF) of HIV⁺ patients, in an attempt to identify GBV-C replication in CSF.

Methods:  This retrospective study involved 22 HIV⁺ patients who underwent a lumbar puncture for diagnostic purposes. To evaluate the prevalence of GBV-C infection in our center, a  control group of 150 HIV⁺ patients was included in the study. GBV-C-RNA was sought in paired plasma, CSF, and PBMC by means of nested polymerase chain reaction (PCR) for 5’UTR. GBV-C genotype was identified by direct sequencing and phylogenetical analysis. GBV-C population in plasma and CSF was characterized by analysis of at least 25 clones for each compartment. HIV load was measured by a quantitative PCR.

Results:  GBV-C RNA was detected in plasma from 37 of 150 (25%) control patients and in the PBMC from 3 of 34 (9%) patients with GBV-C detected in plasma. GBV-C RNA was identified in plasma in 5 of 22 (23%), in none of PBMC, and in 2 of 5 (40%) CSF samples obtained from the 5 GBV-C⁺ patients in plasma. These data showed that the presence of GBV-C RNA in plasma was similar in control group and study population. Albeit GBV-C RNA was detected in 3 PBMC of the control group and in none of the PBMC of the study population, the difference was not statistically significant. Direct sequencing of GBV-C 5’UTR detected in plasma revealed the presence of genotype 2 in 3 patients GBV-C RNA-negative in CSF. Analysis of the GBV-C population within the 5’UTR showed the presence of GBV-C genotype 2 in plasma and genotype 3 in CSF of 1 patient, whereas the other case had mixed infection in plasma (genotype 3/1) and genotype 3 alone in CSF. Plasma HIV RNA levels were significantly higher in patients with CSF positive for GBV-C than in those with GBV-C negative CSF (mean values 5.35 vs 4.39 log copies/mL, p = 0.027). HIV viral load in CSF was similar in all patients (mean values 3.66 vs 3.14 log copies/mL).

Conclusions:  These findings suggest the replication of GBV-C in CSF and the selection of genotype 3 in this compartment. The presence of discordant genotypes in paired plasma/CSF of 1 patient could result from a past mixed infection in plasma.