Hepatitis C virus (HCV) is a major cause of liver diseases including liver cirrhosis and hepatocellular carcinoma. Approximately 3% of the world population is infected with HCV. Thus, HCV infection is considered a public healthy challenge. It is worth mentioning, that the HCV prevalence is dependent on the countries with infection rates around 20% in high endemic countries. The review summarizes recent data on HCV molecular biology, the physiopathology of infection (immune-mediated liver damage, liver fibrosis and lipid metabolism), virus diagnostic and treatment. In addition, currently available in vitro, ex vivo and animal models to study the virus life cycle, virus pathogenesis and therapy are described. Understanding of both host and viral factors may in the future lead to creation of new approaches in generation of an efficient therapeutic vaccine.

Numerous copies of endogenous retroviruses are present in the genome of mammals including man. Although most of them are defective, some, e.g., the human endogenous retroviruses HERV-K, were found to be expressed under certain physiological conditions. For instance, HERV-K is expressed in germ cell tumours and melanomas as well as in the placenta. Most exogenous retroviruses including the human immunodeficiency virus HIV-1 induce severe immunodeficiencies and there is increasing evidence that the transmembrane envelope (TM) proteins of these retroviruses may be involved. We show here that HERV-K particles released from a human teratocarcinoma cell line, a recombinant TM protein and a peptide corresponding to a highly conserved so-called immunosuppressive domain in the TM protein of HERV-K inhibit the proliferation of human immune cells, induce modulation of the expression of numerous cytokines, and modulate the expression of cellular genes as detected by a microarray analysis. The changes in cytokine release and gene expression induced by the TM protein of HERV-K are similar to those found previously induced by the TM protein of HIV-1. These data suggest that the mechanism of immunosuppression may be similar for different retroviruses and that the expression of the TM protein in tumours and in the placenta may suppress immune responses and thus prevent rejection of the tumour and the embryo.

Simian foamy viruses (SFV) are ancient retroviruses of primates and have coevolved with their host species for as many as 30 million years. Although humans are not naturally infected with foamy virus, infection is occasionally acquired through interspecies transmission from nonhuman primates. We show that interspecies transmissions occur in a natural hunter-prey system, i.e., between wild chimpanzees and colobus monkeys, both of which harbor their own species-specific strains of SFV. Chimpanzees infected with chimpanzee SFV strains were shown to be coinfected with SFV from colobus monkeys, indicating that apes are susceptible to SFV superinfection, including highly divergent strains from other primate species.

Viruses, and more particularly retroviruses, have been postulated to play a role in the pathogenesis of autoimmune diseases. In a search for spumaretrovirus infection markers, we screened a group of 29 patients with Graves disease and a representative healthy population (23 subjects) as a control. Southern blot hybridization under stringent conditions, of patients' DNA extracted from peripheral blood lymphocytes, with a spumaretrovirus-specific genomic probe derived from the human spumaretrovirus (HSRV) prototype, gave a positive signal in 10 cases. Moreover, by PCR, HSRV-related sequences were detected in the DNA of 19 patients (66%). Positive DNA samples in Southern blots were also positive in PCR for all regions tested (gag, bel1, bel2, long terminal repeat). Amplified (gag and bel2) products were cloned and sequenced; they showed high homology with HSRV. On the other hand, all 23 control subjects were negative by both procedures. Sera from both populations were examined for the presence of antibodies reactive with antigens of the spumaretrovirus family. These sera were negative by several immunodetection techniques: ELISA, indirect immunofluorescence, serum neutralization, and Western blotting. These results strongly suggest the existence of an association between Graves disease and the presence of HSRV-related infection markers.