N-glycosylation mutations within hepatitis B virus surface major hydrophilic region contribute mostly to immune escape.
J Hepatol
; 60(3): 515-22, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24239777
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.Palavras-chave
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
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Evasão da Resposta Imune
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Antígenos de Superfície da Hepatite B
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Mutação
Limite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article