Hepatitis C virus (HCV), which was identified in 1989 - 1990. Later it was included in new genus Hepacivirus of the family Flaviviridae. Due the genetic heterogeneity of HCV, viral isolates was decided to classificate on genotypes and sybtypes in accordance with the sequence of nucleotides in a certain area of the genome. It was discover that the virus infect only human and chimpanzee. Modern molecular epidemiological data, obtained after 2000, indicate monocentric origin of HCV from Africa, most likely from the central part. Probably, in Africa the conditions for feeling HCV-like virus from unknown non-primate mammal to human were formed. Recently HCV-like viruses were found in dogs, horses, bars, and rodents. The most common hypothesis of the HCV origin base on unknown virus, which is belong to genus Hepacivirus and does not infect human-like primate. The virus is included into group of nonprimate hepacivirus (NPHV). In last centure in our country viral intergenotype recombinant RF_2k/1b was appeared. In modern time HCV diversity can appeared as serology poor displayed forms of the virus. Drug-resistant variants of HCV can accumulate and disseminate again the background of antiviral therapy.
Abstract—
The work is aimed at the synthesis and analysis from NS4A of hepatitis C virus (HCV) antigen peptide fragment that contains a conserved B-cell and T-helper epitopes. The 24-mer peptide VIVGRIILSGRPAVIPDREVLYRK-NH2, which contains the main immunogenic site 24–46 of HCV NS4A antigen (corresponding to the 1681–1703 amino acid residues of the HCV polypeptide), subtype 1b, has been prepared via solid-phase synthesis according to the Fmoc-protocol. Particles with diameters of 73 ± 10 nm (30%) and 236 ± 5 nm (70%) have been detected in the water solution of the highly purified peptide (0.5 mg/mL) by dynamic light scattering. The polydispersity index of 0.377 ± 0.012 implies the existence of heterogeneity because of the aggregation of the peptide molecules. The ζ-potential of the peptide aggregates has been determined as 7.0 ± 0.5 mV by means of electrophoretic light scattering. These data confirm the possibility for the development of a nanoscale liposome form of the peptide preparation. Immunoreactivity of the synthesized highly purified peptide has been studied with the use of blood sera of patients with chronic hepatitis C. Antipeptide immunoglobulins G have been detected in 41.7% of serum samples. Thus, this peptide has been shown to reproduce at least one B-epitope, to which antibodies are raised during natural HCV infection. The synthesized 24-mer peptide is a promising candidate for further research and for use as a potential immunogen for the design of a nanoscale therapeutic immunogenic liposomal peptide composition with synthetic lipids as an adjuvant.
The purpose of the study - to reveal the dependence of the rate of development of liver fibrosis (LF) on genetic factors of hepatitis C virus (HCV) and single nucleotide polymorphisms (SNPs) of the genes of infected people. In the three groups of patients with different rates of development of LF, HCV subtype, viral load, the number of quasi- variant forms and the presence of intergenotype recombinantion, SNPs of human cytokine genes (IL-1ß, IL-6, IL-10, IL-28B, TNF-a , TGF-ß1), hereditary hemochromatosis (HFE), genes involved in the development of endothelial dysfunction (eNOS) and oxidative stress (CYBA) were analyzed. In all groups of patients with HCV subtype 1b prevailed. In the groups with moderate and fast speed of development of LF viral load was revealed to be higher than in the group with the slow development of fibrosis. The number of genetic variants within E2 protein zone in the latter group of patients is characterized to be more than in other groups. Recombinant HCV RNA (2k/1b) was found in the groups with moderate and rapid development of LF. SNP analysis of genes of patients showed a statistically significant relationship between the rapid formation of LF and allelic variants of IL-1ß (-511 TT), IL-10 (-1082 AA), TNF-a (-238 GA or AA) and HFE (S282Y or Y282Y )genes. In other SNPs of analyzed gene there no association with speed of LF was found.
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