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http://www.ncbi.nlm.nih.gov/pubmed/?term=24239777
J Hepatol. 2013 Nov 13. pii: S0168-8278(13)00795-2. doi: 10.1016/j.jhep.2013.11.004. [Epub ahead of print]
N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape.
Yu DM1, Li XH2, Mom V3, Lu ZH4, Liao XW1, Han Y1, Pichoud C3, Gong QM1, Zhang DH1, Zhang Y5, Deny P6, Zoulim F7, Zhang XX8.
Author information
Abstract
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.
Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
KEYWORDS:
AHB, ALT, Acute Hepatitis B, CHB, CMIA, Chronic Hepatitis B, HBV, HBsAg, HCC, Immune escape, LC, MHR, Major hydrophilic region, Mutation, N-glycosylation, PCR, Polymerase chain reaction, aa, amino acid, anti-HBs, anti-HBs antibodies, aspartate aminotransferase, chemiluminescent microparticle enzyme immunoassay, hepatitis B virus, hepatitis B virus surface antigen, hepatocellular carcinoma, liver cirrhosis, major hydrophilic region, rHBsAg, recombinant hepatitis B virus surface antigen
PMID: 24239777 [PubMed - as supplied by publisher] |
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