MOLECULAR GENETICS MUTATIONS OF THE S GENE OF HEPATITIS B HBV VIRUS IN EGYPTIAN PATIENTS
Abstract
Two novel mutants of the hepatitis B virus surface antigen (HBsAg) were characterized. The mutants that were isolated from asymptomatic patients were found to be persistently positive for both HBsAg and anti-hepatitis B surface antibody (anti-HBs) and a long-lasting anti-HBc (core) IgM. Polymerase chain reaction (PCR) and sequencing were performed to surface antigen coding region and revealed two genotype D mutants HBV. Aligned with known HBsAg sequences from GenBank, the mutant variants matched to consensus with eight distinct genotypes (A to H) of hepatitis B virus. Multiple sequence alignment provided a more sensible way of detecting sequence homology and identifying the HBV isolates. From this alignment, certain positions were highly conserved with the previously identified recorded Egyptian isolates, while other positions were not. The importance of the two variants lies in the observation that mutations in the surface antigen coding region can change the immunodominant region structure and therefore alter the group specific determinant antigenicity. Phylogenetic tree based on HBsAg partial nucleotide sequence was displayed. In conclusion, by understanding the HBsAg major immunodominant region nucleotide sequence, highly sensitive diagnostic assays can be achieved for detection of HBV in clinical specimens. Control of these HBV mutants, which will require new drugs, vaccines, and treatment strategies, will become the next major challenge on the path to eventual elimination of HBV infection.References
Abdel-Rahman, N. Z., M. H. Mohamed, Nahed I. Mohamed, Zeinab K. Hassan, Manal, H. El-Sayed, M. K. Mohsen and M. Tarek (2007). Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection. Virology Journal 4: 74 doi: 10.1186/1743-422X-4-74.
Alexander, T., Y. Shiou-Hwie, L. Chun-Jen, C. Claudia and C. Pei-Jer (2008). Viral hepato-carcinogenesis: from infection to cancer. Liver International, 28: 175-188.
De Oliveira, D. E. (2007). DNA viruses in human cancer: an integrated overview on fundamental mechanisms of viral carcinogenesis. Cancer Lett., 247: 182-196.
Ding, X., M. Mizokami, X. Ge, E. Orito, S. Iino, R. Ueda and M. Nakanishi (2002). Different hepatitis B virus genotype distributions among asymptomatic carriers and patients with liver diseases in Nanning, Southern China. Hepatol. Res., 22: 37-44.
Felsenstein, J. (1985). Confidence limits on phylogenies: An approach using the bootstrap. Evolution, 39: 783-791.
Goodarzi, Z., R. Malekzadeh, G. Montazeri, S. M. Alavian, M. Qurbanalizadgan, M. Daram and S. M. Jazayeri (2007). Phylogenetic analysis of HBV based on PreS region in Iranian hepatocellular carcinoma patients. Hepatitis, 7: 201-205.
Kumar, S., K. Tamura, I. B. Jakobsen and M. Nei (2001). Molecular evolutionary genetics analysis software. Tempe, Arizona: Arizona State University.
Manuilov, V. A., L. P. Osipova, I. G. Netesova, E. V. Chub, L. V. Tsoy, R. V. Dul’beev, L. R. Alekseeva, H. Norder, L. O. Magnius and S. V. Netesov (2010). Incidence of genotype of hepatitis B subvirus and HBsAg subtypes in native people of Northern and South Eastern Siberia. Molecular Genetics, Microbiology and Virology, 25: 172-177.
Naito, H., S. Havashi and K. Abe (2001). Rapid and specific genotyping system for hepatitis B virus corresponding to six major genotypes by PCR using type-specific primers. J. Clin. Microbiol., 39: 1686.
Nguyen, T., J. V. Alexander, T. S. Bowden1, C. Croagh, S. Bell, P. V. Desmond, M. Levy and Locarnini S. A. (2009). Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: A perspective on Asia. J. of Hepatology, 52: 508-513.
Ogawa, M., K. Hasegawa, T. Naritomi, N. Torii and N. Hayashi (2002). Clinical features and viral sequences of various genotypes of hepatitis B virus compared among patients with acute hepatitis B. Hepatol. Res., 23: 167-177.
Saudy, N., F. Sugauchi, Y. Tanaka, S. Suzuki, A. Aal, M. A. Zaid, S. Agha and M. Mizokami (2003). Genotypes and phylogenetic characterization of hepatitis B and delta viruses in Egypt. J. Med. Viol., 70: 529-536.
Schaefer, S. (2005). Hepatitis B virus significance of genotypes. J. Viral. Hepat., 12: 111-124.
Stuyver, L., S. De Gendt, C. Van Geyt, F. Zoulim, M. Fried, R. F. Schinazi and R. Rossau (2000). A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. Journal of General Virology, 81: 67-74.
Yalcin, K., H. Degertekin, I. H. Bahcecioglu, A. Demir, M. Aladag, B. Yildirim, S. Horasanli, S. Ciftci and S. Badur (2004). Hepatitis B virus genotype D prevails in patients with persistently elevated or normal ALT levels in Turkey. Infection, 32: 24-29.
Yang, Z., I. J. Lauder and H. J. Lin (1995). Molecular evolution of the hepatitis B virus genome. Journal of Molecular Evolution, 41: 587-596.
Zekri, A. R. N., M. M. Hafez, N. I. Mohamed, Z. K. Hassan, M. H. El-Sayed, M. M. Khaled and T. Mansour (2007). Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection. Virology Journal, 4: 74.