Background: Hepatitis C virus (HCV) infection is common in HIV-1-infected patients. HCV-infected patients are more likely to have changes in their physical and mental well-being than patients with liver disease of other etiology raising the possibility that the virus directly affects the central nervous system (CNS). Importantly, HCV was recently found to replicate in lymphoid cells and macrophages.  To test the hypothesis that HCV can replicate in CNS, we analyzed  autopsy brain tissue samples from 6  HCV-infected patients (3 were HIV+).  To determine whether peripheral blood mononuclear cells (PBMC) could carry HCV across blood-brain barrier, we analyzed HCV RNA in serum, PBMC, and cerebrospinal fluid (CSF) from another group of 9 HCV-infected patients, 6 of whom were HIV+.

Methods: Negative strand HCV RNA, which is a viral replicative intermediary,  was detected with a strand-specific Tth-based RT- PCR and  viral sequences were compared by single-strand conformational polymorphism (SSCP), and sequencing. The analysis was conducted on the 5'untraslated region; genotype differences were confirmed by analysis of the NS5 region.

Results: HCV RNA negative strands were detected in brain tissue in 3 out of 6 patients (1 was HIV+). In 2 of these patients, serum- and brain-derived viral sequences were different and belonged to different genotypes. In 1 of these 2 patients, viral negative strands were detected in  lymph node and, while being different from serum sequences, were  identical to those present in the brain. Negative strand HCV RNA titers in brain tissue were one log lower than titers of the positive strand which is a ratio similar to that found in infected livers. When CSF samples were analyzed, HCV RNA was detected in 6 out of 9 cellular pellets and  in 2  supernatants.  HCV RNA negative strand was detected in CSF cell pellets from 2 HIV+ patients. In 2 patients who were found to harbor different viral strains in serum and PBMC, CSF-derived virus was closely related to PBMC but not to the serum strain, which suggests that HCV-infected lymphoid cells could carry the virus across the blood-brain barrier.

Conclusions:  The results of the present study suggest that HCV can replicate in the central nervous system, although the consequences of this phenomenon are currently unclear. HCV-infected lymphoid cells could carry the virus across the blood-brain barrier into the CNS in a process similar to that postulated for HIV-1.