scholarly journals A quasi-monoclonal anti-HBs response can lead to immune escape of ‘wild-type’ hepatitis B virus

2005 ◽  
Vol 86 (6) ◽  
pp. 1687-1693 ◽  
Author(s):  
Séverine Margeridon ◽  
Alain Lachaux ◽  
Christian Trepo ◽  
Fabien Zoulim ◽  
Alan Kay
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Point Mutation ◽  
Immune Escape ◽  
Humoral Response ◽  
Escape Mutant ◽  
Wild Type ◽  
Hbv Vaccination ◽  
B Virus ◽  
Major Surface

Hepatitis B virus (HBV) infections can be prevented or controlled by the host humoral immune response (anti-HBs) directed against the major surface antigen (HBsAg), elicited either naturally or by vaccination. A chronic HBV carrier was found to have high levels of both virus and anti-HBs. Full-length HBV genomes were amplified from the patient's serum, sequenced and cloned. The genome was ‘wild-type’ HBV of genotype C and serotype adr. The sequence has remained stable, with no signs of emergence of an immune-escape mutant population. To study what was recognized by the patient's serum, viral particles were 35S-labelled and then immunoprecipitated by using the patient's serum or control sera. The patient's serum immunoprecipitated the adr HBsAg encoded by his HBV genome poorly, but efficiently recognized HBsAg of serotype ayw. When his HBV genome was modified by a point mutation to express HBsAg of serotype ayr, the patient's serum could recognize the antigen, as well as the control anti-HBs-positive serum. The patient appeared to have made a quasi-monoclonal humoral response to the y epitope. By switching to the d epitope, which requires only a point mutation, the virus could replicate, despite the high levels of anti-HBs. This study underlines the subtleties of virus–host interactions. Implications for HBV vaccination are discussed.

scholarly journals Genetic Characterization of Hepatitis B Virus in Peripheral Blood Leukocytes: Evidence for Selection and Compartmentalization of Viral Variants with the Immune Escape G145R Mutation

2009 ◽  
Vol 83 (19) ◽  
pp. 9983-9992 ◽  
Author(s):  
Sibnarayan Datta ◽  
Rajesh Panigrahi ◽  
Avik Biswas ◽  
Partha K. Chandra ◽  
Arup Banerjee ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Peripheral Blood ◽  
Immune Escape ◽  
Escape Mutant ◽  
Large Set ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Frequent Event ◽  
B Virus

ABSTRACT The compartmentalization of viral variants in distinct host tissues is a frequent event in many viral infections. Although hepatitis B virus (HBV) classically is considered hepatotropic, it has strong lymphotropic properties as well. However, unlike other viruses, molecular evolutionary studies to characterize HBV variants in compartments other than hepatocytes or sera have not been performed. The present work attempted to characterize HBV sequences from the peripheral blood leukocytes (PBL) of a large set of subjects, using advanced molecular biology and computational methods. The results of this study revealed the exclusive compartmentalization of HBV subgenotype Ae/A2-specific sequences with a potent immune escape G145R mutation in the PBL of the majority of the subjects. Interestingly, entirely different HBV genotypes/subgenotypes (C, D, or Aa/A1) were found to predominate in the sera of the same study populations. These results suggest that subgenotype Ae/A2 is selectively archived in the PBL, and the high prevalence of G145R indicates high immune pressure and high evolutionary rates of HBV DNA in the PBL. The results are analogous to available literature on the compartmentalization of other viruses. The present work thus provides evidence in favor of the compartment-specific abundance, evolution, and emergence of the potent immune escape mutant. These findings have important implications in the field of HBV molecular epidemiology, transmission, transfusion medicine, organ transplantation, and vaccination strategies.

scholarly journals Endocytosis of Hepatitis B Immune Globulin into Hepatocytes Inhibits the Secretion of Hepatitis B Virus Surface Antigen and Virions

2003 ◽  
Vol 77 (16) ◽  
pp. 8882-8892 ◽  
Author(s):  
Ralf Schilling ◽  
Samreen Ijaz ◽  
Michail Davidoff ◽  
Jia Yee Lee ◽  
Stephen Locarnini ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Immune Escape ◽  
Dependent Manner ◽  
Wild Type ◽  
Virus Surface ◽  
Virus Surface Antigen ◽  
B Virus ◽  
Specific Igg

ABSTRACT Hepatitis B immunoglobulin is used for prophylaxis against hepatitis B virus (HBV) and is thought to act by neutralization of virions and hepatitis B virus surface antigen (HBsAg)-containing particles in circulation. Using a panel of hepatocyte-derived cell lines, the present study investigated in vitro whether HBs-specific immunoglobulin G (IgG) is internalized in hepatocytes and whether it interacts with HBsAg in the cells. By immunoelectron microscopy and immunoblotting, human IgG and FcRn receptor for IgG were demonstrated on cellular membranes and in cytoplasmic extracts, irrespective of the HBsAg status of the cells. Furthermore, HBsAg and anti-HBs were shown to be colocalized in the same cellular compartment by two-color confocal microscopy. Endocytosis of HBs-specific IgG caused intracellular accumulation of HBsAg in a dose-dependent manner and inhibited the secretion of HBsAg and HBV virions from the cells. These effects were not observed with F(ab)2 fragments or nonimmune IgG as controls. The specificity of intracellular HBsAg- anti-HBs interaction was further investigated in cells transfected with HBV genomes expressing wild-type HBsAg or immune escape HBsAg (with a G145R mutation). Monoclonal anti-HBs markedly reduced the secretion of wild-type HBsAg, while the secretion of mutant HBsAg was not affected. These results suggest that HBs-specific IgG binds to hepatocytes and interacts with HBsAg within the cells. This may be relevant for the selection of surface antibody escape mutations.

scholarly journals Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation

2012 ◽  
Vol 87 (4) ◽  
pp. 2352-2357 ◽  
Author(s):  
K. Kwei ◽  
X. Tang ◽  
A. S. Lok ◽  
C. Sureau ◽  
T. Garcia ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Envelope Proteins ◽  
Wild Type ◽  
Site Mutation ◽  
B Virus ◽  
Escape Mutants

A new immune escape mutant of hepatitis B virus with an Asp to Ala substitution in aa144 of the envelope major protein

1995 ◽  
Vol 146 (6) ◽  
pp. 397-407 ◽  
Author(s):  
F. Ni ◽  
D. Fang ◽  
R. Gan ◽  
Z. Li ◽  
S. Duan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Escape ◽  
Escape Mutant ◽  
Major Protein ◽  
B Virus

scholarly journals Analysis of the Physicochemical Properties, Replication and Pathophysiology of a Massively Glycosylated Hepatitis B Virus HBsAg Escape Mutant

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2328
Author(s):  
Md. Golzar Hossain ◽  
Yadarat Suwanmanee ◽  
Kaili Du ◽  
Keiji Ueda
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Physicochemical Properties ◽  
Antiviral Drug ◽  
Glycosylation Site ◽  
Escape Mutant ◽  
Wild Type ◽  
Coding Region ◽  
B Virus ◽  
Secretion Efficiency

Mutations in HBsAg, the surface antigen of the hepatitis B virus (HBV), might affect the serum HBV DNA level of HBV-infected patients, since the reverse transcriptase (RT) domain of HBV polymerase overlaps with the HBsAg-coding region. We previously identified a diagnostic escape mutant (W3S) HBV that produces massively glycosylated HBsAg. In this study, we constructed an HBV-producing vector that expresses W3S HBs (pHB-W3S) along with a wild-type HBV-producing plasmid (pHB-WT) in order to analyze the physicochemical properties, replication, and antiviral drug response of the mutant. Transfection of either pHB-WT or W3S into HepG2 cells yielded similar CsCl density profiles and eAg expression, as did transfection of a glycosylation defective mutant, pHB-W3S (N146G), in which a glycosylation site at the 146aa asparagine (N) site of HBs was mutated to glycine (G). Virion secretion, however, seemed to be severely impaired in cases of pHB-W3S and pHB-W3S (N146G), compared with pHB-WT, as determined by qPCR and Southern blot analysis. Furthermore, inhibition of glycosylation using tunicamycinTM on wild-type HBV production also reduced the virion secretion. These results suggested that the HBV core and Dane particle could be formed either by massively glycosylated or glycosylation-defective HBsAg, but reduced and/or almost completely blocked the virion secretion efficiency, indicating that balanced glycosylation of HBsAg is required for efficient release of HBV, and mutations inducing an imbalanced glycosylation of HBs would cause the virion to become stuck in the cells, which might be associated with various pathogeneses due to HBV infection.

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