Molecular Epidemiology of Hepatitis C Virus Genotype 4 Isolates in Egypt and Analysis of the Variability of Envelope Proteins E1 and E2 in Patients with Chronic Hepatitis

Abstract

We analyzed hepatitis C virus (HCV) genotype 4 isolates circulating in the Alexandria District (Egypt) in terms of genetic divergence and the presence of different subtypes. Hypervariable region 1 (HVR1) and the NH2 region of the E2 protein were characterized, and the heterogeneity of subtype 4a isolates was evaluated by analyzing epitope frequencies, immunoproteasome prediction, and possible glycosylation patterns. The heterogeneity of the nucleotide sequences was greater than that found in previous studies, which reported only subtype 4a. Subtype 4a was most common (78% of cases), yet four new subtypes were found, with subtype 4m representing 11% of the cases and the other three subtypes representing another 11%. Substantial heterogeneity was also found when the intrasubtype 4a sequences were analyzed. Differences in the probability of glycosylation and in the positions of the different sites were also observed. The analysis of the predicted cytotoxic-T-lymphocyte epitopes showed differences in both the potential proteosome cleavage and the prediction score. The Egyptian isolates in our study also showed high variability in terms of the HVR1 neutralization epitope. Five of these isolates showed amino acid substitutions never previously observed (a total of six positions). Four of these residues (in four different isolates) were in positions involved in anchoring to the E2 glycoprotein core and in maintaining the HVR1 conformation. The results of this study indicate that HCV genotype 4 in Egypt is extremely variable, not only in terms of sequence, but also in terms of functional and immunological determinants. These data should be taken into account in planning the development of vaccine trials in Egypt.Hepatitis C virus (HCV) is the major etiological agent of chronic hepatitis and liver disease worldwide, and it is a major cause of morbidity and mortality. In 80% of cases, infection with HCV results in chronic hepatitis, possibly leading to cirrhosis and hepatocellular carcinoma (11,28).HCV is characterized by a high degree of nucleotide sequence variability. Overall, the heterogeneity of the viral genome ranges from 30 to 35% between different genotypes, although it varies with the specific region of the genome, and it has been used to define three types of regions: highly conserved regions (e.g., the 5Ј untranslated region), variable regions (e.g., envelope 1 [E1] and nonstructural 5b [NS5b]), and hypervariable regions (HVR) (e.g., HVR1 and HVR2 in E2) (48). Furthermore, because of errors of the RNA-dependent RNA polymerase, HCV has a high rate of mutation during replication, and it exists in the bloodstreams of infected persons as complex distributions of mutants known as viral quasispecies, which fluctuate during the course of the disease, mainly as a result of immune pressure (47,51,54). These coexisting mutant genomes always have a consensus, or master, sequence. In general, despite the potentially high mutation rate and variability of RNA viruses, changes in the consensus sequence of a viral population ...

Prevalence of occult hepatitis C in egyptian patients with non alcoholic fatty liver disease

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Evaluation of Multiplex Nested Polymerase Chain Reaction for Routine Hepatitis C Virus Genotyping in Egyptian Patients

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Single nucleotide polymorphisms of interleukins associated with hepatitis C virus infection in Egypt

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