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Background/Aims: Hepatitis B virus (HBV) continues to be one of the most important viral pathogens in humans. Surface (S) protein is the major HBV antigen that mediates virus attachment and entry and determines the virus subtype. Mutations in S gene, particularly in the “a” determinant, can influence virus detection by ELISA and may generate escape mutants. Since no records have documented the S gene mutations in HBV strains circulating in Saudi Arabia, the current study was designed to study sequence variation of S gene in strains circulating in Saudi Arabia and its correlation with clinical and risk factors. Patients and Methods: A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis. Patients and Methods: A total of 123 HBV-infected patients were recruited for this study. Clinical and biochemical parameters, serological markers, and viral load were determined in all patients. The entire S gene sequence of samples with viral load exceeding 2000 IU/mL was retrieved and exploited in sequence and phylogenetic analysis. Results: A total of 48 mutations (21 unique) were recorded in viral strains in Saudi Arabia, among which 24 (11 unique) changed their respective amino acids. Two amino acid changes were recorded in “a” determinant, including F130L and S135F with no evidence of the vaccine escape mutant G145R in any of the samples. No specific relationship was recognized between the mutation/amino acid change record of HBsAg in strains in Saudi Arabia and clinical or laboratory data. Phylogenetic analysis categorized HBV viral strains in Saudi Arabia as members of subgenotypes D1 and D3. Conclusion: The present report is the first that describes mutation analysis of HBsAg in strains in Saudi Arabia on both nucleotide and amino acid levels. Different substitutions, particularly in major hydrophilic region, may have a potential influence on disease diagnosis, vaccination strategy, and antiviral chemotherapy.

This study investigated how HBV replication and host immune response are effected by reduced expression of TGF-β1 and HBx.Short interfering RNA (siRNA) knockdown technology has been used to examine the role of TGF-β1 in hepatitis B virus replication. The siTGF-β1 has been transfected along with 1.3mer HBV x-null to investigate the knockdown effect of TGF-β1 on HBV replication and host immune factors.In this study, we found that diminished expression of TGF-β1 and increased expression of HBx enhances HBV replication several folds. The differential expression of TGF-β1 and HBx also stimulated transcriptional viral replicative intermediate (pgRNA) and secretion of core and 'e' antigen at translational level. Consequently, several cytokines such as IL-2, IL-8 and chemokine monocyte- chemoattractant protein (MCP-1) were increased significantly in response to stimulation of HBV replication. In contrast, TNF-α and RANTES mRNA expression increased insignificantly in response to enhanced HBV replication.We concluded that reduced expression of TGF-β1 together with HBx expression stimulate HBV replication and immune response, although the underlying mechanism of stimulation most likely differs.