Mutations in the S gene region of hepatitis B virus genotype D in Golestan Province-Iran

Abstract

Mutations of HBsAg especially within the "a" determinant could alter the antigenicity of the protein causing failure of HBsAg neutralization and escaping from the host's immune system, resulting in active viral replication and liver disease. This project aimed to investigate mutation in the S gene region of HBV infected patients in Golestan Province-Iran. HBV-DNA extractions from plasma and PCR of 100 patients were performed. Direct sequencing and alignment of S gene were applied using reference sequence from Gene Bank database. All isolates were belonged to genotype D, subgenotype D1, subtype ayw2. Overall 92 point mutations occurred. Of them, 40 (43.47%) were missense and 52 (56.52%) were silent. Mutations were detected in 95 cases (95%). Five of 40 mutations (12.5%) occurred in "a" determinant and 13 (32.5%), 17 (42.5%), and 2 (5%) were seen in antigenic epitope regions of B cell, CD 4 + and CTL, respectively. Frame shift mutations were seen in 22 cases (22%). 14% of mutations occurred at Major Hydrophilic Region(MHR) area which P120T/S and R122K/T substitutions were the most frequent ones (4%). Mutation in G145R of the S gene was observed in one case. A large number of MHR mutants are in association with failure of HBsAg detection, vaccine, and immunotherapy escape. This study showed "a" determinant S gene mutations in HBV infected people with HBsAg positivity in Golestan Province-Iran. The rate of mutation in our study was 95%. Collectively, the results of this project exhibited that most of mutations were clustered in CD 4 + antigenic epitopes. © Springer Science+Business Media, LLC 2012

Hepatitis B virus reactivation in HBsAg-negative patients is associated with emergence of viral strains with mutated HBsAg and reverse transcriptase

“…2000; Yong- Lin et al, 2012;Simon et al, 2013;Yao et al, 2013;Pezzano et al, 2011;Baclig et al, 2014;Lee et al, 2005;Moradi et al, 2012;Lin et al, 2013;Salpini et al, 2015). In contrast, two substitutions N131A observed here in a patient whose serum sample tested HBsAg-negative at time of HBV-R (pt 10) and S136F (pt 5) were not, to our knowledge, previously described.…”

Naturally Occurring Surface Antigen Variants of Hepatitis B Virus in Tunisian Patients

“…This finding was in agreement with the results of other studies, especially in genotype D-infected patients [22,56]. In our study group, nearly half of the mutations (44.3%) occurred in the CTL epitope, suggesting a narrowly focused immune selection pressure at a hot spot position.…”

Genotyping and Mutation Pattern in the Overlapping MHR Region of HBV Isolates in Southern Khorasan, Eastern Iran

“…Of course, part of it may be related to the small sample size. In another study in Iran, P120T/S and R122K/T were found in 4% of patients, and G145R was found only in one case (13); which none of them occurred in the current project. These mutations frequently occurred and it was suggested that this frequency may be due to the pressure of the immune system or vaccine on their selection, considering the fact that these patients did not receive NAs.…”

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