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

Abstract

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.

• Authors: Nada Vasiljević, Ljiljana Marković
• Journal: Medicinski pregled (Med Pregl) 2005 Nov-Dec Vol. 58 Issue 11-12 Pg. 582-6 ISSN: 0025-8105 [Print] Serbia
• PMID: 16673863 (Publication Type: Journal Article)

Chemical References

• Hepatitis Antigens
• MAS1 protein, human
• Proto-Oncogene Mas
• Hepatocyte Growth Factor
• Nitric Oxide Synthase
• Protein-Tyrosine Kinases
• HGF activator
• Serine Endopeptidases

Topics

• Autoimmunity
• Cross Reactions
• Hepacivirus (genetics)
• Hepatitis Antigens (genetics)
• Hepatitis C (immunology, transmission)
• Hepatocyte Growth Factor (genetics)
• Humans
• Nitric Oxide Synthase (genetics)
• Protein-Tyrosine Kinases (genetics)
• Proto-Oncogene Mas
• Sequence Homology, Amino Acid
• Serine Endopeptidases (genetics)
• Transfusion Reaction