scholarly journals Hepatitis B Virus Covalently Closed Circular DNA Interacting HBx and HBc Proteins Global Conservancy Analysis and Related B or T lymphocyte Epitopes

2021 ◽  
Author(s):  
Umar Saeed ◽  
Zahra Zahid Piracha ◽  
Rizwan Uppal
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
T Cell Epitopes ◽  
Mhc I ◽  
Circular Dna ◽  
Consensus Sequences ◽  
Global Consensus ◽  
Mhc Ii ◽  
Hbv Genotypes ◽  
B Virus

Abstract Background:The Hepatitis B Virus HBx and HBc proteins associate with covalently closed circular DNA, which is the main reason for intrahepatic viral persistence and major cause due to which HBV cure has not been achieved yet. The aims of present study were to generate HBV genotype-specific consensus sequences of HBx and HBc, align all ten (A to J) consensus sequences to develop global consensus sequences of HBx and HBc, analyze variable and conserved motifs, and to predict highly conserved B and T cell binding epitopes in HBx and HBc proteins, respectively.Methods:237 HBx and 207 HBc sequences, belonging to all HBV genotypes reported globally, were aligned in CLC main workbench to draw global consensus sequences and phylogenetic analysis was performed. The location of possible B cell epitopes were analyzed using immune Epitope Database (IEDB), while possible T cell epitopes were analyzed using ProPred-I and ProPred in-silico prediction tools. Results:The HBx residues 52H to 59P, which are important for augmentation effect in HBV replication and 137C, which is crucial for transactivation of HBx are conserved in all HBV genotypes. The HBc residues 141S to149V, which are crucial for pre-genomic RNA packaging, viral DNA synthesis and virion secretion are highly conserved across all the genotypes of HBV. The HBx related epitopes X-B2 and X-B4, and HBc related C-B6 and C-B7 epitopes could be important candidates for B-cell based vaccine. Among HBx related MHC-I epitopes X-M2, X-M5, X-M8, X-M11, X-M12, X-M20, X-M22, X-M25, X-M27 and X-M32, and MHC-II epitopes the X-T4, X-T6 and X-T8 could be important targets for vaccine development. While among HBc related MHC-I epitopes C-M1, C-M2, C-M4, C-M6-11, C-M13, C-M19, C-M24-26, C-M30, C-M34-36, C-M40 and C-M43-45, and MHC-II epitopes the C-T1-3, C-T9, C-T10, C-T12, C-T14 and C-T16-18 epitopes could be ideal epitopes with high conservancy across all HBV genotypes. Conclusion:The analysis will aid in screening of novel anti-HBV agents and designing of site-specific inhibitors which may show response against all genotypes. Also the predicted B- or T cell epitopes might be effective for designing antibodies against all majorly occurring genotypes of HBV across the world.

scholarly journals Discovery and Selection of Hepatitis B Virus-Derived T Cell Epitopes for Global Immunotherapy Based on Viral Indispensability, Conservation, and HLA-Binding Strength

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 ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Viral Replication ◽  
Immune Escape ◽  
The Novel ◽  
T Cell Epitopes ◽  
Infected Population ◽  
B Virus ◽  
Hla Binding

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.

In vivo hierarchy of immunodominant and subdominant HLA-A*0201-restricted T-cell epitopes of HBx antigen of hepatitis B virus

2005 ◽  
Vol 7 (4) ◽  
pp. 626-634 ◽  
Author(s):  
Silvina Malmassari ◽  
Yu Chun Lone ◽  
Menghua Zhang ◽  
Catherine Transy ◽  
Marie-Louise Michel
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Epitopes ◽  
B Virus

scholarly journals Identification of immunodominant T cell epitopes of the hepatitis B virus nucleocapsid antigen.

1991 ◽  
Vol 88 (1) ◽  
pp. 214-222 ◽  
Author(s):  
C Ferrari ◽  
A Bertoletti ◽  
A Penna ◽  
A Cavalli ◽  
A Valli ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
T Cell Epitopes ◽  
B Virus

Mutations of T-Cell Epitopes in the Hepatitis B Virus Surface Gene in Children With Chronic Infection and Hepatocellular Carcinoma

2008 ◽  
Vol 103 (4) ◽  
pp. 1004-1009 ◽  
Author(s):  
Yen-Hsuan Ni ◽  
Mei-Hwei Chang ◽  
Hong-Yuan Hsu ◽  
Yi-Ching Tung ◽  
Huey-Ling Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Chronic Infection ◽  
T Cell Epitopes ◽  
Virus Surface ◽  
B Virus ◽  
Surface Gene

scholarly journals Identification of a Promiscuous Conserved CTL Epitope Within the SARS-CoV-2 Spike Protein

2021 ◽  
Author(s):  
Sheng Jiang ◽  
Shuting Wu ◽  
Gan Zhao ◽  
Yue He ◽  
Xinrong Guo ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Response ◽  
Spike Protein ◽  
Target Antigen ◽  
T Cell Epitopes ◽  
Global Public Health ◽  
Mhc I ◽  
Mhc Ii ◽  
Ctl Epitope ◽  
Infected Cells

Abstract The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC‑I and MHC‑II epitopes by ELIspot and cytolytic assays to a conserved MHC‑I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

scholarly journals Hepatitis B virus polymerase-specific T cell epitopes shift in a mouse model of chronic infection

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Mohadeseh Hasanpourghadi ◽  
Mikhail Novikov ◽  
Dakota Newman ◽  
ZhiQuan Xiang ◽  
Xiang Yang Zhou ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Checkpoint Inhibitor ◽  
Public Health Problem ◽  
T Cell Responses ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Chronic Hepatitis B Virus ◽  
B Virus

Abstract Background Chronic hepatitis B virus (HBV) infection (CHB) is a significant public health problem that could benefit from treatment with immunomodulators. Here we describe a set of therapeutic HBV vaccines that target the internal viral proteins. Methods Vaccines are delivered by chimpanzee adenovirus vectors (AdC) of serotype 6 (AdC6) and 7 (AdC7) used in prime only or prime-boost regimens. The HBV antigens are fused into an early T cell checkpoint inhibitor, herpes simplex virus (HSV) glycoprotein D (gD), which enhances and broadens vaccine-induced cluster of differentiation (CD8)+ T cell responses. Results Our results show that the vaccines are immunogenic in mice. They induce potent CD8+ T cell responses that recognize multiple epitopes. CD8+ T cell responses increase after a boost, although the breadth remains similar. In mice, which carry high sustained loads of HBV particles due to a hepatic infection with an adeno-associated virus (AAV)8 vector expressing the 1.3HBV genome, CD8+ T cell responses to the vaccines are attenuated with a marked shift in the CD8+ T cells’ epitope recognition profile. Conclusions Our data show that in different stains of mice including those that carry a human major histocompatibility complex (MHC) class I antigen HBV vaccines adjuvanted with a checkpoint inhibitor induce potent and broad HBV-specific CD8+ T cell responses and lower but still detectable CD4+ T cell responses. CD8+ T cell responses are reduced and their epitope specificity changes in mice that are chronically exposed to HBV antigens. Implications for the design of therapeutic HBV vaccines are discussed.

Identification of T-cell epitopes associated with immunity within the surface protein of duck hepatitis B virus

2006 ◽  
Vol 13 (8) ◽  
pp. 515-522 ◽  
Author(s):  
R. Welschinger ◽  
Y. Cossart ◽  
J. Pouliopoulos ◽  
R. Dixon ◽  
K. Vickery
Keyword(s):  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Surface Protein ◽  
T Cell Epitopes ◽  
Duck Hepatitis B Virus ◽  
Duck Hepatitis ◽  
B Virus

scholarly journals Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

2021 ◽  
Author(s):  
Sheng Jiang ◽  
Shuting Wu ◽  
Gan Zhao ◽  
Yue He ◽  
Xinrong Guo ◽  
...  
Keyword(s):  
T Cell ◽  
Cellular Response ◽  
Spike Protein ◽  
Target Antigen ◽  
T Cell Epitopes ◽  
Global Public Health ◽  
Mhc I ◽  
Mhc Ii ◽  
Ctl Epitope ◽  
Infected Cells

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC I and MHC II epitopes by ELIspot and cytolytic assays to a conserved MHC I epitope. The epitope is highly conserved in current viral variants and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

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