ABSTRACT
BACKGROUND AND OBJECTIVES: Iranian chronic HBV carrier's population has shown a unique pattern of genotype D distribution all around the country. The aim of this study was to explore more details of evolutionary history of carriers based on structural surface proteins from different provinces. MATERIALS AND METHODS: Sera obtained from 360 isolates from 12 Different regions of country were used for amplification and sequencing of surface proteins. A detailed mutational analysis was undertaken. RESULTS: The total ratio for Missense/Silent nucleotide substitutions was 0.96. Sistan and Kermanshah showed the lowest rate of evolution between provinces (P = 0.055). On the other hand, Khorasan Razavi and Khoozestan contained the highest ratio (P = 0.055). The rest of regions were laid between these two extremes. Azarbayjan and Guilan showed the highest proportion of immune epitope distribution (91.3% and 96%, respectively). Conversely, Sistan and Tehran harbored the least percentage (66.6% and 68.8%, respectively). Kermanshah province contained only 5.2%, whereas Isfahan had 54.5% of B cell epitope distribution. In terms of T helper epitopes, all provinces showed a somehow homogeneity: 22.58% (Fars) to 46.6% (Khuzestan). On the other hand, distribution of substitutions within the CTL epitopes showed a wide range of variation between 6.6% (Khuzestan) and 63% (Kermanshah). CONCLUSION: Further to low selection pressure found in Iranian population, the variations between different regions designate random genetic drift within the surface proteins. These finding would have some applications in terms of specific antiviral regimen, design of more efficient vaccine and public health issues.
ABSTRACT
OBJECTIVE S: The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients. MATERIALS AND METHODS: 16 patients received the HBV vaccine and another 16 individuals from the control group did not. The surface gene was amplified and directly sequenced from samples prior to vaccination and six months after the third dose. RESULTS: Only one patient lost HBsAg. 48 and 44 amino acid mutations were found before and after vaccine therapy in the vaccine group respectively, 51 of which (55.4%) occurred in immune epitopes: 5 were in B cell, 21 in T helper (Th), and 25 in cytotoxic T-lymphocyte (CTL) epitopes. In the control group, 35 and 41 amino acid substitutions were found before and after therapy, respectively. 32 (42%) of 76 amino acid changes occurred within immune epitopes. There were no differences in age, gender, and duration of chronicity in both patient and control groups in terms of the frequency and the patterns of mutations. CONCLUSION: In chronic carriers who already had HBsAg variants selected by the host-immune response, any immune stimulation by the vaccine had no effect on the chronic state of these patients or selected any remarkable escape mutants. Newer strategies should be considered based on third generation or the use of DNA vaccines or new adjuvants.
ABSTRACT
BACKGROUND: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. OBJECTIVES: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. MATERIALS AND METHODS: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. RESULTS: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. CONCLUSIONS: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.
