CTL escape mutations of core protein are more frequent in strains of HBeAg negative patients with low levels of HBV DNA

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• 作者：Hossein Sendi ; Marjan Mehrab-Mohseni ; Saeid Shahraz ; Helene Norder ; Seyed-Moayed Alavian ; Babak Noorinayer ; Mohammad R. Zali ; Paul Pumpens ; Herbert L. Bonkovsky ; Lars O. Magnius
• 刊名：Journal of Clinical Virology
• 出版年：2009
• 出版时间：November 2009
• 年：2009
• 卷：46
• 期：3
• 页码：259-264
• 全文大小：1117 K

文摘

Background

Recent studies have suggested that Cytotoxic T lymphocytes (CTL) play a key role in eliminating hepatitis B virus (HBV).

Objectives

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).

Study design

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.

Results

Amino acid mutations of core protein were observed more frequently in HBV strains from ASCs than e-CHB patients (p = 0.014). Asn⁶⁷ mutation was mutually exclusive to the combination Ile⁶⁶ and Ser⁶⁹ (P < 0.001). Substitutions for Ser²¹ and Thr12Ser were associated with lower serum levels of HBV DNA (p < 0.001). None of the patients with mutations in HLA-A2 CTL epitope, 18–27, had serum HBV DNA more than 10⁵ copies/mL (p < 0.001). By multivariate analysis, high level (>10⁵ 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 T¹⁷⁶²A¹⁷⁶⁴ mutations together with G¹⁷⁵⁷ (OR: 16.87, p = 0.004).

Conclusion

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.