This study examined the relationships between hepatitis C virus (HCV) genotypes and the routes of HCV transmission in 101 patients with chronic hepatitis C. Patients who received blood transfusions (43%) and those with chronic hepatitis C of unknown cause (37%) had similar mean ages, age distribution, and HCV genotype distribution (1a, 19% vs. 14%; 1b, 52% vs. 54%; 3a, 10% vs. 9%; other, 19% vs. 23%). Intravenous drug users (IVDUs) were significantly younger and had a different genotype distribution (1a, 33%; 1b, 0; 3a, 63%; other, 5%; P < .001). Transmission of HCV 3a has been observed only over the past 20 years; other genotypes were transmitted up to 40 years ago. These results suggest that for 20 years there have been two independent ongoing hepatitis C epidemics. One affects persons who received blood transfusions or whose source of infection is unknown. These persons are older and are mainly infected by HCV 1b. The second type of infection occurs in IVDUs and infects younger persons, mainly with HCV 3a.

Constitutive activation of the nuclear factor-kappaB (NF-kappaB) pathway has been shown to be involved in the resistance of tumor cells to apoptosis in several human malignancies of the hematopoietic lineage. By using electrophoretic mobility shift assay (EMSA) and confocal microscopic analysis, we demonstrate that NF-kappaB is constitutively activated in cutaneous T-cell lymphoma (CTCL) cell lines HuT-78, MyLa, and SeAx and in peripheral blood lymphocytes (PBLs) from patients with Sézary syndrome (SS) presenting a high ratio of tumor cells, with evidence of p50 and RelA/p65 in DNA-linked complexes. Transfection of SeAx line with a kappaB/luciferase reporter plasmid showed that translocated NF-kappaB complexes were functional. Selective inhibition of NF-kappaB, by transfecting CTCL cell lines with a super-repressor form of IkappaB alpha, led to apoptosis. We evidenced down-regulation of NF-kappaB activation and induction of CTCL cell apoptosis in the presence of proteasome 26S inhibitors ALLN, MG132, and bortezomib. Bortezomib at nanomolar concentrations inhibited constitutive activation of NF-kappaB and induced apoptosis of CTCL cells, with evidence of an upregulation of Bax expression. These results demonstrate the key role played by NF-kappaB in the resistance of CTCL to apoptosis and suggest that bortezomib might be useful for the treatment of patients with advanced stages of CTCL refractory to standard antineoplastic chemotherapy.

Our results suggest that antiviral therapy with protease inhibitors are clinically efficient in HIV-associated Kaposi's sarcoma and that there exists a correlation between clinical response and negation of HHV-8 viraemia.