Genetic variability of hepatitis B virus "a" determinant in Iranian isolates

Abstract number: R2488

Mohebbi S.R., Zali N., Amini-Bavil-Olyaee S., Derakhshan F., Chiani M., Rostaminejad M., Sabahi F., Zali M.R.

Objectives: Hepatitis B virus (HBV) persistently infects more than 350 million people worldwide and can induce a spectrum of acute and chronic liver diseases. Because HBV is a DNA virus with a reverse transcription step, it is subject to a high mutation rate. HBsAg is the primary diagnostic marker for HBV infection. The "a" determinant of HBsAg is a highly conformational, immunodominant antigenic determinant and is common to all subtypes. There is very limited knowledge about the genetic variability of HBV strains circulating in the population of Iranian HBV infected patients. The aim of this study was to determine HBV subtypes and to analyse mutations in HBV "a" determinant among chronically infected patients from different regions of Iran.

Methods: 249 sera from HBV infected patients living in different regions of Iran were collected between January 2004 and July 2007. Serological markers of HBV infection were determined by available commercially ELISA kits. A 402 bp fragment of the HBV S gene including the "a" determinant was amplified, sequenced and then subjected for genetic variability analysis. Subtypes were also predicted from the sequence encoding the HBsAg by identifying the amino acids encoded at specific positions.

Results: The majority of Iranian isolates were ayw2 (239/249, 94.4%). Five isolates were ayw3 (2%), Seven isolates were ayw1 (2.8%) and One was detected as ayw4 (0.4%). Interestingly, one isolate was unknown subtype because it had atypical substitution at subtype specifying residues (127S). Various point mutations in the sequence of HBsAg have been found among Iranian HBV isolates. The most common escape mutant amongst Iranian patients was S143L (5.2%) and P120S (1.6%), T118A (0.8%), S136Y (0.8%) and T118K (0.8%) ranked next. Other mutations were also found with minor prevalence (0.4%) as P120T, T123N, T126S, A128V, G130N, P142L, D144E, G145R and P153Q.

Conclusion: Amino acid substitutions within the "a" determinant can lead to conformational changes. Some of these changes may cause important medical and public health issues such as vaccine escape, failure of hepatitis B immune globulin treatment in liver transplant patients, and failure of commercially available immunoassays to detect infected individuals. Our results showed high prevalence of HBsAg mutants in HBV infected Iranian patients and these mutants may play a role in HBV evolution against mass vaccination.