期刊
JOURNAL OF HEPATOLOGY
卷 60, 期 3, 页码 515-522出版社
ELSEVIER
DOI: 10.1016/j.jhep.2013.11.004
关键词
HBsAg; Major hydrophilic region; N-glycosylation; Immune escape; Mutation
资金
- National Natural Science Foundation of China [81171616]
- Science & Technology Commission of Shanghai Municipality [09ZR1418800]
- Major National S&T Projects for Infectious Diseases [2012ZX10002007, 2013ZX10002001]
- Program of International Science & Technology Cooperation of Shanghai Municipality [11410701700, 12410707200]
- State Major Basic Research Program (973) of China [2012CB519000]
- International Science & Technology Cooperation Program of China [2012DFG32190]
- French agency for research against AIDS and hepatitis (ANRS)
- Programme Conjoint de Recherche MIRA of Region Rhone-Alpes
- Abbott Laboratories
Background & Aims: HBV immune escape represents a challenge to prevention, diagnosis, and treatment of hepatitis B. Here, we analyzed the molecular and clinical characteristics of HBV immune escape mutants in a Chinese cohort of chronically infected patients. Methods: Two hundred sixteen patients with HBsAg and anti-HBs were studied, with one hundred eighty-two HBV carriers. without anti-HBs as a control group. Recombinant HBsAg bearing the most frequent N-glycosylation mutations were expressed in CHO and HuH7 cells. After confirming N-glycosylation at the most frequent sites (129 and 131), together with inserted mutations, functional analysis were performed to study antigenicity and secretion capacity. Results: One hundred twenty-three patients had the wild-type HBs gene sequence, 93 patients (43%) had mutants in the major hydrophilic region (MHR), and 47 of the 93 patients had additional N-glycosylation mutations, which were transmitted horizontally to at least 2 patients, one of whom was efficiently vaccinated. The frequency of N-glycosylation mutation in the case group was much higher than that of the control group (47/216 vs. 1/182). Compared with wild-type HBsAg, HBsAg mutants reacted weakly with anti-HBs using a chemiluminescent microparticle enzyme immunoassay. Native gel analysis of secreted virion in supernatants of transfected HuH7 cells indicated that mutants had better virion enveloping and secretion capacity than wild-type HBV. Conclusions: Our results suggest that specific HBsAg MHR N-glycosylation mutations are implicated in HBV immune escape in a high endemic area. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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