Dissection of two drug-targeted regions of Hepatitis C virus subtype 4a infecting Egyptian patients.

Recently, treatment of HCV infection has been improved after the development of direct acting antivirals (DAAs) which target different viral proteins (NS3-4A, NS5A and NS5B). The activity and effectiveness of these DAAs are affected by the presence of resistance associated substitutions (RASs). This study aimed to characterize HCV genotypes circulating among Egyptian HCV patients, to dissect the full sequences of HCV NS3-4A and NS5B regions, and to characterize RASs associated with NS3-4A and NS5B inhibitors in HCV treatment-naïve patients. Genotyping of 80 HCV samples from treatment-naïve patients was done using restriction fragment length polymorphism and phylogenetic analysis based on some full NS5B sequences. Results showed the prevalence of HCV subtype 4a. Twenty four new full sequences of NS3-4A and NS5B regions of subtype 4a were deposited in the GenBank database. In general, the substitutions associated with NS3-4A-targeting drugs were absent predicting possible responsiveness of Egyptian HCV patients to these drugs. In addition, the absence of amino acid substitutions associated with resistance to Sofosbuvir may predict good response to treatment with Sofosbuvir. Some amino acid substitutions associated with resistance to different classes of non-nucleoside inhibitors were detected. Further investigations on treated Egyptian HCV patients may evaluate the effectiveness of the massively used drugs. Many predicted T-cell-binding epitopes in NS3-4A and NS5B regions were found to be highly conserved in the currently studied isolates; a finding that might be important for HCV vaccine development. We demonstrated potential NS3 epitopes that could be used in engineering T cells against HCV epitopes.

5' UTR and NS5B-based genotyping of hepatitis C virus in patients from Damietta governorate, Egypt.

Chronic hepatitis C virus (HCV) infection is a main health problem in Egypt causing high rates of mortalities. Egypt has the highest HCV prevalence in the world, with specific HCV subtypes epidemic and circulating extensively in the country. Different antiviral therapy protocols have been implemented for treating Egyptian HCV patients. Due to the limited data about HCV in Egypt, this study aimed to genotype HCV strains circulating in the Nile Delta Damietta governorate and to investigate the variation in the nonstructural 5B (NS5B) region targeted by the newly approved antiviral drugs. Thirty HCV samples from treatment-naïve patients were genotyped by restriction fragment length polymorphism. Some samples were genotyped by direct sequencing of their 5' untranslated region (UTR) and NS5B regions. Phylogenetic analysis was also performed on the sequences of their NS5B regions. Fourteen new sequences have been deposited in the GenBank database. Results showed that subtype 4a was prevalent in addition to subtype 1g. None of the previously reported NS5B substitutions were detected in the sequenced isolates from treatment-naïve patients, which may be a good predictor for efficient treatment of HCV Egyptian patients with Sofosbuvir. Further studies on Sofosbuvir treated-HCV Egyptian patients are required to investigate whether any NS5B substitutions can confer resistance to treatment.

TNF-α gene polymorphisms and expression.

Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine with an important role in the pathogenesis of several diseases. Its encoding gene is located in the short arm of chromosome 6 in the major histocompatibility complex class III region. Most of the TNF-α gene polymorphisms are located in its promoter region and they are thought to affect the susceptibility and/or severity of different human diseases. This review summarizes the data related to the association between TNF-α gene and its receptor polymorphisms, and the development of autoimmune diseases. Among these polymorphisms the -308G/A TNF-α promotor polymorphism has been associated several times with the the development of autoimmune diseases, however some discrepant results have been recorded. The other TNF-α gene polymorphisms had little or no association with autoimmune diseases. Current results about the molecules controlling TNF-α expression are also presented. The discrepancy between different records could be related partly to either the differences in the ethnic origin or number of the studied individuals, or the abundance and activation of other molecules that interact with the TNF-α promotor region or other elements.