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[Gene similarity between hepatitis C virus and human proteins--a blood transfusion problem].

Medicinski Pregled 2005 November
INTRODUCTION: Hepatitis C is a post-transfusion hepatitis which causes serious problems in blood transfusion. Blood testing requires highly sensitive and specific assays with high predictive value.

GENOMIC CHARACTERISTICS OF HEPATITIS C VIRUS: According to recommendations of International Association for the study of Liver Diseases etiological diagnosis of hepatitis is based on highly sensitive third generation assays: epitopes in the NS5 region comprising noncoding sequence UTR with 324-341 well conserved pair of homologous basis in 92% HCV genomes, therefore appropriate for virus RNA detection.

DEVELOPMENT OF ASSAYS FOR HEPATITIS VIRUS: The first generation of immunoenzyme tests (IET) were based on detection of antibodies on antigen c 100-3, which is a part of the NS4 region of HCV genome. The second generation of tests with two recombinant proteins--c22-3 and c200, achieved higher sensitivity of assays. The third generation included epitopes from NS5 region, and removed the antigen c100-3.

DEVELOPMENT OF AUTOIMMUNITY: Autoimmunity is a pathophysiological mechanism that's leads to chronic inflammatory diseases. Autoimunity is characterized by loss of tolerance towards self-antigens. Viral hepatitis C is associated with development of autoimmune phenomena.

MOLECULAR MIMICRY: Molecular mimicry, as a mechanism of autoimmunity, was investigated to establish cross-Reactive immune reactions between HCV antigen and human nitrogen-oxide synthase, Tyrosine kinase Lck and hepatic growth factor activator.

CROSS REACTIVITY BETWEEN HCV PROTEINS AND HUMAN PROTEINS: HCV capsid proteins initiate the autoimmune process in the liver because of cross reaction of antibodies with human Gor protein 19-27, which causes autoimmune chronic hepatitis. However, analysis of human protein from protein basis Swiss-prot shows homology between NS5 region and 3 human protein nitrogen oxide synthases, tyrosine kinase-Lck, proto-oncogene and hepatic growth factor activator. According to protein data analysis and competitive in vitro experiments, it was concluded that presence of auto-antibodies is probably the consequence of cross reactive immune response.

CONCLUSION: Homology of amino acid sequences in the NS5 region of the HCV genome with nitrogen-oxide synthase, tyrosine kinase-Lck, and hepatic growth factor activator, causes auto-immune phenomena in HC, and can be a model for researching autoimmunity and human virus-induced autoimmune diseases.

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