TT virus (TTV) loads associated with the peripheral blood cells of seven patients known to carry the virus in plasma were investigated by real-time PCR. Whereas red cells/platelets were uniformly negative, six and four patients yielded positive peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes, respectively, but viral titres were generally low. Fractionation of PBMCs into monocyte- and B, T4, and T8 lymphocyte-enriched subpopulations showed no pattern in the viral loads that might suggest the preferential association of TTV to one or more specific cell types. TTV-negative PBMCs absorbed measurable amounts of virus when incubated with infected plasma at 4 degrees C. Furthermore, cultures of TTV-negative phytohaemagglutinin-stimulated PBMCs exposed in vitro to virus-positive plasma and faecal extracts released considerable levels of infectious TTV into the supernatant fluid and the same was true for TTV-positive stimulated PBMCs. These results indicate that, whereas freshly harvested resting PBMCs seem to produce little, if any TTV, stimulated PBMCs actively replicate the virus.

Hepatitis C virus (HCV) exists in vivo as a highly variable mixture of closely related genomes (quasispecies), but the pathogenetic significance of such heterogeneity is still largely unknown. To investigate this issue, we compared the composition of HCV quasispecies found in the liver, peripheral blood mononuclear cells (PBMC) and plasma of ten patients by single-strand conformation polymorphism analysis of the E2/NS1 region and sequencing of the variants detected. We found considerable quasispecies differences between the liver and PBMC in all the patients, involving variant numbers, relative quantities and relative electrophoretic mobilities, but no apparent tissue-specific trend. Genome variants present in the liver and/or PBMC were not detected in the corresponding plasma samples, while certain HCV variants were present only in plasma. No dominant amino acids or amino acid pattern characteristic of variants present solely in the PBMC were detected in the E2/NS1 region sequenced.Hepatitis C virus (HCV) exists within infected hosts as a variably complex system of related genomes (quasispecies) generated by the limited fidelity of RNA replication. Recent evidence has shown that quasispecies composition exhibits extensive variation within individual isolates (Okada et al., 1992) and can vary spontaneously both over time (Kao et al., 1995) and with liver disease progression . In addition, the extent of HCV quasispecies diversity has been reported to be predictive of responsiveness to interferon treatment (Moribe et al., 1995) and to decrease markedly

The pathogenic potential of the newly discovered TT virus (TTV) is currently a matter of conjecture. Its presence was investigated in the serum of 660 patients, by polymerase chain reaction. TTV was detected in 50% of 221 patients with unselected pathologies, and no significant differences related to age, sex, or organ disease were noted. TTV was present at a significantly higher rate in hemophiliacs (73%) and at lower rates in patients with cirrhosis (30%) and rheumatoid arthritis (28%). Patients with other liver diseases, systemic lupus erythematosus, or psoriasis or receiving hemodialysis had rates of infection similar to those in unselected patients. TTV-positive patients treated with interferon-alpha for underlying type C hepatitis showed no appreciable changes of TTV viremia levels. Type 1b was by far the most frequent viral genotype (92%), followed by types 2c (5%) and 1a (3%).

Hepatitis C virus (HCV) is a leading cause of liver damage and has also been implicated in extrahepatic pathologies. We examined for HCV RNA paired CSF and plasma samples from 12 viremia positive patients using PCR. The CSF from 5/5 HIV-infected patients and 5/7 HIV-negative patients were HCV RNA positive. Branched DNA analysis showed that HCV loads in CSF were much lower than in plasma. Several HCV-positive CSF showed no evidence of blood contamination, impaired blood-brain barrier, or intrathecal IgG production. Comparison of HCV quasispecies in three sets of samples suggested that the virus in CSF was of plasma origin

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