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      Subgenotypes and Mutations in the S and Polymerase Genes of Hepatitis B Virus Carriers in the West Bank, Palestine


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          The mutation rate and genetic variability of hepatitis B virus (HBV) are crucial factors for efficient treatment and successful vaccination against HBV. Until today, genetic properties of this virus among the Palestinian population remain unknown. Therefore, we performed genetic analysis of the overlapping S and polymerase genes of HBV, isolated from 40 Palestinian patients' sera. All patients were HBsAg positive and presented with a viral load above 10 5 HBV genome copies/ml. The genotyping results of the S gene demonstrated that HBV D1 was detected in 90% of the samples representing the most prominent subgenotype among Palestinians carrying HBV. Various mutations existed within the S gene; in five patients four known escape mutations including the common G145R and D144E were found. Furthermore, a ratio of 4.25 of non-synonymous to synonymous mutations in the S gene indicated a strong selection pressure on the HBs antigen loops of HBV strains circulating in those Palestinian patients. Although all patients were treatment-naïve, with the exception of one, several mutations were found in the HBV polymerase gene, but none pointed to drug resistance. The study presented here is the first report to address subgenotypes and mutation analyses of HBV S and polymerase genes in Palestine.

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          Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes.

          Sequences of 234 complete genomes and 631 hepatitis B surface antigen genes were used to assess the worldwide diversity of hepatitis B virus (HBV). Apart from the described two subgenotypes each for A and F, also B, C, and D divided into four subgenotypes each in the analysis of complete genomes supported by significant bootstrap values. The subgenotypes of B and C differed in their geographical distribution, with B1 dominating in Japan, B2 in China and Vietnam, B3 confined to Indonesia, and B4 confined to Vietnam, all strains specifying subtype ayw1. Subgenotype C1 was common in Japan, Korea, and China; C2 in China, South-East Asia, and Bangladesh, and C3 in the Oceania comprising strains specifying adrq-, and C4 specifying ayw3 is encountered in Aborigines from Australia. This pattern of defined geographical distribution was less evident for D1-D4, where the subgenotypes were widely spread in Europe, Africa, and Asia, possibly due to their divergence having occurred a longer time ago than for genotypes B and C, with D4 being the first split and still the dominating subgenotype of D in the Oceania. The genetic diversity of HBV and the geographical distribution of its subgenotypes provide a tool to reconstruct the evolutionary history of HBV and may help to complement genetic data in the understanding of the evolution and past migrations of man. 2004 S. Karger AG, Basel.
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            To determine the frequency of vertical transmission of hepatitis B antigen (HB5 Ag) from asymptomatic carrier mothers in Taiwan to their offspring, HB5 Ag was sought by radioimmunoassay and complement fixation. Of 158 babies born to carrier mothers, antigenemia developed in 63; 51 of these antigenemic babies had become antigen positive within the six months of life. Three inter-related factors were found to increase the risk that antigenemia would develop in the infant: a high maternal complement-fixation titer for HB5 Ag: presence of HB5 Ag in the baby's umbilical-cord blood: and antigenemia in siblings. In contrast to previous studies, these findings indicate that vertical transmission from carrier mothers frequently occurs, at least in Taiwan, and may partially explain Taiwan's high prevalence of HB5 Ag.
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              Vaccine-induced escape mutant of hepatitis B virus.

              In southern Italy, 44 contacts of hepatitis B virus carriers, including infants of carrier mothers, became HBsAg positive despite passive and active immunisation according to standard protocols. In 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. In 1 infant, serious disease occurred. The virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. A point mutation from guanosine to adenosine at nucleotide position 587 resulted in an aminoacid substitution from glycine to arginine in the highly antigenic a determinant of HBsAg. This mutation is stable: it is present in an isolate from the child 5 years later. In some of these patients, including this child, the a determinant, to which a large part of the vaccine-induced immunity is directed, has been partly lost. Binding to HBsAg of a monoclonal antibody, previously mapped to the region of the mutation, was reduced in the child relative to that of the mother.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                12 December 2014
                : 9
                : 12
                : e113821
                [1 ]Virology Research Laboratory, Medical Research Center, Al-Quds University, Abu Dies-East Jerusalem, Palestine
                [2 ]Al-Makassed Islamic Charitable Hospital (MICH) Central Laboratory, East Jerusalem, Palestine
                [3 ]Institute of Medical Virology, Justus-Liebig University Giessen, National Reference Center for Hepatitis B and D Viruses, German Center for Infection Research (DZIF), Biomedical Research Center, Giessen, Germany
                Yonsei University College of Medicine, Republic of Korea
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ZA MA. Performed the experiments: ZA NS. Analyzed the data: ZA MA. Contributed reagents/materials/analysis tools: MA DG SB. Wrote the paper: MA.

                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                : 17 January 2014
                : 31 October 2014
                Page count
                Pages: 16
                This research was supported by German Research Foundation (DFG) grant No. GL595/2-1.
                Research Article
                Biology and Life Sciences
                Applied Microbiology
                Computational Biology
                Medical Microbiology
                Microbial Pathogens
                Viral Transmission and Infection
                Viral Vaccines
                Microbial Mutation
                Plant Science
                Plant Pathology
                Infectious Disease Epidemiology
                Medicine and Health Sciences
                Clinical Epidemiology
                Gastroenterology and Hepatology
                Liver Diseases
                Infectious Hepatitis
                Health Care
                Primary Care
                Infectious Diseases
                Viral Diseases
                Public and Occupational Health
                Women's Health



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