Study of Genotype, Subtype and Mutation in the S Gene in Hepatitis B Patients Co-infected with HIV in Iran

Abstract

Background: Co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) is common due to shared routes of transmission, as reported approximately 10% of 33 million HIV-infected patients worldwide are chronically infected with HBV. 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. This results in active viral replication and liver disease. Objectives: The aim of the survey was to identify HBV genotype and subtype, and different mutations in HBV S gene in hepatitis B patients co-infected with HIV in Iran. Methods: PCR performance and HBV-DNA extraction from plasma of 124 samples obtained from treatment naive HIV/HBV coinfected participants were according to the protocol. Direct sequencing and alignment of surface gene were carried out using reference sequences from the Gene Bank database. Results: From 124 HIV/HBV ELISA positive samples, 40 were HBV DNA-positive. Themean age of patients was 33.88 years. 20% of them were female and 80% were male. All isolates belonged to the sub genotype D1/ayw2 and genotype D. There were 50 point mutations including 23 (46%) missense and 27 (54%) silent mutations in amino acid level. Twenty three amino acid mutations occurred in different immune epitopes such as 11 (47.82%) in B cell, 6 (26.08%) in T helper and 2 (%8.6) in CTL. The prevalence of mutations in both “a” determinant region and Major Hydrophilic Region (MHR) was 5 (21.73%). Conclusions: Our findings showed that P127T and A70P (Outside of MHR) were the most frequently occurring substitution mutations. P127T, P132T, G130R, and S136Y substitutions placed in the first loop of the “a” determinant and the other substitutions of P142T and D144N occurred in the second loop of “a” determinant. The results of our study showed that most of the mutations occurred in B cell epitopes. The mutation in a surface gene of HBV may be selected by immune pressure or anti-retroviral therapy. Keywords: HIV, HBV, Co-infection, S Gene, Mutation