scholarly journals Hypermodification and Immune Escape of an Internally Deleted Middle-Envelope (M) Protein of Frequent and Predominant Hepatitis B Virus Variants

Virology ◽  
2002 ◽  
Vol 292 (1) ◽  
pp. 44-58 ◽  
Author(s):  
Pei-Ching Tai ◽  
Fat-Moon Suk ◽  
Wolfram H. Gerlich ◽  
A.Robert Neurath ◽  
Chiaho Shih
2014 ◽  
Vol 60 (3) ◽  
pp. 515-522 ◽  
Author(s):  
De-Min Yu ◽  
Xin-Hua Li ◽  
Vannary Mom ◽  
Zhong-Hua Lu ◽  
Xiang-Wei Liao ◽  
...  

2021 ◽  
Vol 21 ◽  
Author(s):  
Hassan Akrami ◽  
Mohammad Rafiee Monjezi ◽  
Shahrzad Ilbeigi ◽  
Farshid Amiri ◽  
Mohammad Reza Fattahi

: Hepatitis B virus [HBV], the best-described hepadnavirus, distributed all around the world and may lead to chronic and acute liver disease, cirrhosis, and hepatocellular carcinoma. Despite the advancement in treatment against HBV, an error-prone reverse transcriptase which is require for HBV replication as well as host immune pressure lead to constant evolution and emergence of genotypes, sub-genotypes and mutant viruses; so, HBV will be remained as a major healthcare problem around the world. This review article mainly focuses on the HBV mutations which correlated to occult HBV infection, Immune scape, vaccine failure and eventually liver cirrhosis and HCC. Current study indicated that preS/S region mutations are related to vaccine failure, immune escape, occult HBV infection and the occurrence of HCC. Whereas, P region Mutations may lead to drug resistance to NA antivirals. PreC/C region mutations are associated to HBeAg negativity, immune escape, and persistent hepatitis. Moreover, X region Mutations play an important role in HCC development.


2019 ◽  
Vol 94 (7) ◽  
Author(s):  
Monique T. A. de Beijer ◽  
Diahann T. S. L. Jansen ◽  
Yingying Dou ◽  
Wim J. E. van Esch ◽  
Juk Yee Mok ◽  
...  

ABSTRACT Immunotherapy represents an attractive option for the treatment of chronic hepatitis B virus (HBV) infection. The HBV proteins polymerase (Pol) and HBx are of special interest for antigen-specific immunotherapy because they are essential for viral replication and have been associated with viral control (Pol) or are still expressed upon viral DNA integration (HBx). Here, we scored all currently described HBx- and Pol-derived epitope sequences for viral indispensability and conservation across all HBV genotypes. This yielded 7 HBx-derived and 26 Pol-derived reported epitopes with functional association and high conservation. We subsequently predicted novel HLA-binding peptides for 6 HLA supertypes prevalent in HBV-infected patients. Potential epitopes expected to be the least prone to immune escape were subjected to a state-of-the-art in vitro assay to validate their HLA-binding capacity. Using this method, a total of 13 HLA binders derived from HBx and 33 binders from Pol were identified across HLA types. Subsequently, we demonstrated interferon gamma (IFN-γ) production in response to 5 of the novel HBx-derived binders and 17 of the novel Pol-derived binders. In addition, we validated several infrequently described epitopes. Collectively, these results specify a set of highly potent T cell epitopes that represent a valuable resource for future HBV immunotherapy design. IMPORTANCE Multiple HBV-derived T cell epitopes have been reported, which can be useful in a therapeutic vaccination strategy. However, these epitopes are largely restricted to HLA-A*02, which is not dominantly expressed in populations with high HBV prevalence. Thus, current epitopes are falling short in the development of a global immunotherapeutic approach. Therefore, we aimed to identify novel epitopes for 6 HLA supertypes most prevalent in the infected population. Moreover, established epitopes might not all be equally effective as they can be subject to different levels of immune escape. It is therefore important to identify targets that are crucial in viral replication and conserved in the majority of the infected population. Here, we applied a stringent selection procedure to compose a combined overview of existing and novel HBV-derived T cell epitopes most promising for viral eradication. This set of T cell epitopes now lays the basis for the development of globally effective HBV antigen-specific immunotherapies.


2009 ◽  
Vol 83 (19) ◽  
pp. 9983-9992 ◽  
Author(s):  
Sibnarayan Datta ◽  
Rajesh Panigrahi ◽  
Avik Biswas ◽  
Partha K. Chandra ◽  
Arup Banerjee ◽  
...  

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.


2008 ◽  
Vol 198 (11) ◽  
pp. 1620-1624 ◽  
Author(s):  
Cornelia Henke‐Gendo ◽  
Samad Amini‐Bavil‐Olyaee ◽  
Deepthi Challapalli ◽  
Christian Trautwein ◽  
Heidi Deppe ◽  
...  

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