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J Clin Virol. 2017 Sep;94:115-122. doi: 10.1016/j.jcv.2017.08.001. Epub 2017 Aug 5.

The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection.

Author information

1
Université de Lorraine, EA 7300 Stress, Immunité, Pathogènes, Vandoeuvre-les-Nancy, F-54505, France. Electronic address: marine.eschlimann@hotmail.fr.
2
Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: b.malve@chru-nancy.fr.
3
Université de Lorraine, EA 7300 Stress, Immunité, Pathogènes, Vandoeuvre-les-Nancy, F-54505, France; Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: aurelie.velay@chru-strasbourg.fr.
4
Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: h.fenaux@chru-nancy.fr.
5
Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: s.berger@chru-nancy.fr.
6
Université de Lorraine, EA 7300 Stress, Immunité, Pathogènes, Vandoeuvre-les-Nancy, F-54505, France. Electronic address: jean-pol.frippiat@univ-lorraine.fr.
7
Université de Lyon, Unité Inserm UI1052, Lyon, F-69424, France. Electronic address: fabien.zoulim@inserm.fr.
8
Centre Hospitalier Universitaire de Nancy, Service d'Hépato-gastroentérologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: mouni.bensenane@yahoo.fr.
9
Centre Hospitalier Universitaire de Nancy, Service d'Hépato-gastroentérologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: jp.bronowicki@chru-nancy.fr.
10
Centre Hospitalier Universitaire de Nancy, Service des Maladies Infectieuses et Tropicales, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: f.goehringer@chru-nancy.fr.
11
Centre Hospitalier Universitaire de Nancy, Service des Maladies Infectieuses et Tropicales, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: t.may@chru-nancy.fr.
12
Université de Lorraine, EA 7300 Stress, Immunité, Pathogènes, Vandoeuvre-les-Nancy, F-54505, France; Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: h.jeulin@chru-nancy.fr.
13
Université de Lorraine, EA 7300 Stress, Immunité, Pathogènes, Vandoeuvre-les-Nancy, F-54505, France; Centre Hospitalier Universitaire de Nancy, Laboratoire de Virologie, Vandoeuvre-les-Nancy, F-54511, France. Electronic address: e.schvoerer@chru-nancy.fr.

Abstract

BACKGROUND:

More than 240 million people are chronically infected by hepatitis B virus (HBV) worldwide. Envelope proteins play a crucial role in viral cellular entry and immune recognition. The loss of HBs antigen (HBsAg) correlated with a good clinical prognosis is rarely achieved with or without treatment (3-16%).

OBJECTIVES:

HBV envelope variability was investigated according to HBsAg persistence.

STUDY DESIGN:

The cohort consisted of 15 HBV genotype A-infected patients divided into "resolvers", with HBsAg clearance, and "non-resolvers", with HBsAg persistence and in subgroups: acute (n=5, AHBV) or chronic infection (n=4, CHBV) and HBV/HIV coinfection (n=6, CHBV/HIV). HBV S and preS sequences were studied by direct and ultra-deep sequencing. Amino acid sequences were analyzed with bioinformatics for predicted antigenicity.

RESULTS:

In S gene, the complexity was lower in AHBV than in chronic-infected patients (p=0.046). Major mutations, detected using direct sequencing, were more frequent in AHBV developing chronicity (p=0.01) than in AHBV resolvers. In the Major Hydrophilic Region, more frequent mutations were observed in non-resolvers versus resolvers (p=0.047) and non-resolvers tended to have more haplotypes with a reduced predicted antigenicity (p=0.07). Most of the mutations in preS/S region were found rather in epitopic than in non-epitopic areas (p=0.025). Interestingly, the mutation sY161F found in 3/8 non-resolvers was associated with a decrease in predicted antigenicity (28%; AnTheProt).

CONCLUSIONS:

HBsAg persistence was correlated with mutations and deletions in areas playing a key role in immune recognition. These data suggest that variability in HBV envelope could favor immune escape in various clinical settings of HBV genotype A-infected patients.

KEYWORDS:

Deletions; HBV preS/S variability; HBV/HIV coinfection; Hepatitis B virus; Immune escape

PMID:
28822954
DOI:
10.1016/j.jcv.2017.08.001
[Indexed for MEDLINE]

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