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.

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.

Precore/Core Promoter Mutant Hepatitis B Virus Produces More Severe Histologic Liver Disease than Wild Type Hepatitis B Virus

2007 ◽  
Vol 1 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Mamun-Al-Mahtab ◽  
Salimur Rahman ◽  
Mobin Khan ◽  
Ayub Mamun ◽  
Kamal
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Wild Type ◽  
B Virus ◽  
Promoter Mutant

scholarly journals Analysis of the complete genome of hepatitis B virus subgenotype C2 isolate NHB17965 from a HBV infected patient

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1023 ◽  
Author(s):  
Modhusudon Shaha ◽  
Palash Kumar Sarker ◽  
Md. Saddam Hossain ◽  
Keshob Chandra Das ◽  
Munira Jahan ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Complete Genome ◽  
Infected Patient ◽  
Surface Proteins ◽  
Wild Type ◽  
Small Surface ◽  
Chronic Hepatitis B Virus ◽  
B Virus ◽  
Complete Genome Analysis

The burden of chronic hepatitis B virus (HBV) infections is increasingly detected nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from a HBV infected patient. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. This study may help clinicians and scientists gain in-depth knowledge on the current substitutions of HBV/C2 genome and to identify potential therapies against HBV infections.

scholarly journals Anti-Hepatitis B Virus Activity of Esculetin from Microsorium fortunei In Vitro and In Vivo

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3475 ◽  
Author(s):  
Si-Xin Huang ◽  
Jun-Fei Mou ◽  
Qin Luo ◽  
Qing-Hu Mo ◽  
Xian-Li Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Hepatitis B Surface Antigen ◽  
Antiviral Drug ◽  
Liver Carcinoma ◽  
Dependent Manner ◽  
Duck Hepatitis ◽  
B Virus

Coumarins are widely present in a variety of plants and have a variety of pharmacological activities. In this study, we isolated a coumarin compound from Microsorium fortunei (Moore) Ching; the compound was identified as esculetin by hydrogen and carbon spectroscopy. Its anti-hepatitis B virus (HBV) activity was investigated in vitro and in vivo. In the human hepatocellular liver carcinoma 2.2.15 cell line (HepG2.2.15) transfected with HBV, esculetin effecting inhibited the expression of the HBV antigens and HBV DNA in vitro. Esculetin inhibited the expression of Hepatitis B virus X (HBx) protein in a dose-dependent manner. In the ducklings infected with duck hepatitis B virus (DHBV), the levels of DHBV DNA, duck hepatitis B surface antigen (DHBsAg), duck hepatitis B e-antigen (DHBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) decreased significantly after esculetin treatment. Summing up the above, the results suggest that esculetin efficiently inhibits HBV replication both in vitro and in vivo, which provides an opportunity for further development of esculetin as antiviral drug.

scholarly journals The Synthetic Antiviral Drug Arbidol Inhibits Globally Prevalent Pathogenic Viruses

2016 ◽  
Vol 90 (6) ◽  
pp. 3086-3092 ◽  
Author(s):  
Eve-Isabelle Pécheur ◽  
Viktoriya Borisevich ◽  
Peter Halfmann ◽  
John D. Morrey ◽  
Donald F. Smee ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Ebola Virus ◽  
Antiviral Drug ◽  
Human Herpesvirus ◽  
Influenza Viruses ◽  
Human Herpesvirus 8 ◽  
Herpesvirus 8 ◽  
B Virus

ABSTRACTArbidol (ARB) is a synthetic antiviral originally developed to combat influenza viruses. ARB is currently used clinically in several countries but not in North America. We have previously shown that ARB inhibitsin vitrohepatitis C virus (HCV) by blocking HCV entry and replication. In this report, we expand the list of viruses that are inhibited by ARB and demonstrate that ARB suppressesin vitroinfection of mammalian cells with Ebola virus (EBOV), Tacaribe arenavirus, and human herpesvirus 8 (HHV-8). We also confirm suppression of hepatitis B virus and poliovirus by ARB. ARB inhibited EBOV Zaire Kikwit infection when added before or at the same time as virus infection and was less effective when added 24 h after EBOV infection. Experiments with recombinant vesicular stomatitis virus (VSV) expressing the EBOV Zaire glycoprotein showed that infection was inhibited by ARB at early stages, most likely at the level of viral entry into host cells. ARB inhibited HHV-8 replication to a similar degree as cidofovir. Our data broaden the spectrum of antiviral efficacy of ARB to include globally prevalent viruses that cause significant morbidity and mortality.IMPORTANCEThere are many globally prevalent viruses for which there are no licensed vaccines or antiviral medicines. Some of these viruses, such as Ebola virus or members of the arenavirus family, rapidly cause severe hemorrhagic diseases that can be fatal. Other viruses, such as hepatitis B virus or human herpesvirus 8 (HHV-8), establish persistent infections that cause chronic illnesses, including cancer. Thus, finding an affordable, effective, and safe drug that blocks many viruses remains an unmet medical need. The antiviral drug arbidol (ARB), already in clinical use in several countries as an anti-influenza treatment, has been previously shown to suppress the growth of many viruses. In this report, we expand the list of viruses that are blocked by ARB in a laboratory setting to include Ebola virus, Tacaribe arenavirus, and HHV-8, and we propose ARB as a broad-spectrum antiviral drug that may be useful against hemorrhagic viruses.

Sign in / Sign up

Export Citation Format

Share Document