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EN
Hepatitis C virus (HCV) is a major human pathogen that causes mild to severe liver disease worldwide. This positive strand RNA virus is remarkably efficient at establishing chronic infections. In order for a noncytopathic virus such as HCV to persist, the virus must escape immune recognition or evade host immune surveillance. Immune escape via the hypervariable region of the E2 envelope protein has been postulated as one mechanism for HCV persistent infection. Such hypervariability within the E2 protein may be under selective pressure from protective B cell or T cell responses and be able to escape immune recognition by rapid mutation of antigenic site. In addition to antigenic variation, HCV may also suppress immune response, leading to dampening of cellular immunity. This is supported by recent studies in our laboratory demonstrating that the HCV core protein can suppress host immune responses to vaccinia virus by downregulating viral specific cytotoxic T lymphocyte (CTL) responses and cytokine production. An understanding of the mechanisms behind HCV persistence will provide a basis for the rational design of vaccines and novel therapeutic agents targeting human HCV infection.
EN
There is a strong epidemiologic relationship between chronic hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), although the cellular and molecular mechanisms of tumor formation remain to be firmly established. Clearly, HCV is associated with the development of chronic hepatitis and cirrhosis, so that it may contribute to hepatocarcinogenesis as a consequence of its central role in the appearance and progression of necroinflammatory liver disease. There is also increasing evidence for a direct contribution of several HCV gene products to the development of the transformed phenotype, although none of the putative mechanisms involved in tumor formation have been strongly supported by in vivo evidence. Even if HCV is not shown to be a complete carcinogen, it may act as a cocarcinogen with underlying (serologically negative) hepatitis B virus (HBV) infection, in the context of alcoholic cirrhosis, and in patients with long term exposure to chemical hepatocarcinogens such as aflatoxin B1.
EN
Hepatitis C virus belongs to the group of particularly dangerous and most extensively studied RNA viruses. Since no vaccine for HCV is known and post-exposure treatment of infected patients has not been yet optimal, novel therapeutic strategies are being developed very intensively. Oligonucleotide-based molecular tools such as antisense oligonucleotides, ribozymes, DNAzymes, aptamers and interfering RNAs are proving as effective modulators of gene expression and potential therapeutics. Several examples of oligonucleotide-based molecular tools directed towards HCV viral RNA are discussed in this review.
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