CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA
| Autor: | Herbert L. Bonkovsky, Babak Noorinayer, Hossein Sendi, Marjan Mehrab-Mohseni, Mohammad Reza Zali, Saeid Shahraz, Paul Pumpens, Lars O. Magnius, Seyed Moayed Alavian, Helene Norder |
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| Rok vydání: | 2009 |
| Předmět: |
Models
Molecular Hepatitis B virus Molecular Sequence Data Biology medicine.disease_cause Article Epitopes Orthohepadnavirus Virology medicine Cytotoxic T cell Humans Amino Acid Sequence Hepatitis B e Antigens Chi-Square Distribution virus diseases Hepatitis B biology.organism_classification medicine.disease Hepatitis B Core Antigens digestive system diseases HBcAg CTL Infectious Diseases Logistic Models Hepadnaviridae HBeAg Immunology Carrier State DNA Viral Multivariate Analysis Mutation Sequence Alignment T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 46(3) |
| ISSN: | 1873-5967 |
| Popis: | Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).We aimed to investigate the role of mutations in different immune epitopes of hepatitis B core antigen (HBcAg) among Iranians with hepatitis B e antigen negative chronic hepatitis B (e-CHB), and asymptomatic carriers (ASCs).Amino acids 1-150 of HBcAg were characterized for HBV strains from 29 e-CHB patients and 48 ASCs from Iran. All patients were infected with HBV genotype D and had previously been investigated for the presence of pre-core and basic core promoter (BCP) mutants.Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p=0.014). Asn(67) mutation was mutually exclusive to the combination Ile(66) and Ser(69) (P0.001). Substitutions for Ser(21) and Thr12Ser were associated with lower serum levels of HBV DNA (p0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18-27, had serum HBV DNA more than 10(5)copies/mL (p0.001). By multivariate analysis, high level (10(5)copies/mL) of serum HBV DNA was inversely associated with the presence of mutations in CTL epitopes of HBc (OR: 0.11, p=0.015), while it was directly associated with the presence of promoter double T(1762)A(1764) mutations together with G(1757) (OR: 16.87, p=0.004).The inverse correlation between serum levels of HBV DNA and CTL escape mutations of the core protein in HBeAg seroconverted patients, supports the notion that selection of CTL escape mutations consolidates the persistence of HBV infection despite reducing viral fitness. |
| Databáze: | OpenAIRE |
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