scholarly journals Differential presentation of endogenous and exogenous hepatitis B surface antigens influences priming of CD8+T cells in an epitope-specific manner

2014 ◽  
Vol 44 (7) ◽  
pp. 1981-1991 ◽  
Author(s):  
Petra Riedl ◽  
Michael Reiser ◽  
Katja Stifter ◽  
Jana Krieger ◽  
Reinhold Schirmbeck
Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2273
Author(s):  
Katrin Manske ◽  
Annika Schneider ◽  
Chunkyu Ko ◽  
Percy A. Knolle ◽  
Katja Steiger ◽  
...  

Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal models. Here, we describe the generation of a recombinant adenovirus expressing an HBV 1.3-overlength genome linked to luciferase (Ad-HBV-Luc) allowing for precise analysis of the quantity of infected hepatocytes. This enables sensitive and close-meshed monitoring of HBV-specific CD8 T cells and the onset of anti-viral immunity in mice. A high dose of Ad-HBV-Luc developed into chronic hepatitis B accompanied by dysfunctional CD8 T cells characterized by high expression of PD1 and TOX and low expression of KLRG1 and GzmB. In contrast, a low dose of Ad-HBV-Luc infection resulted in acute hepatitis with CD8 T cell-mediated elimination of HBV-replicating hepatocytes associated with elevated sALT levels and increased numbers of cytotoxic HBV-specific CD8 T cells. Thus, the infectious dose was a critical factor to induce either acute self-limited or chronic HBV infection in mice. Taken together, the new Ad-HBV-Luc vector will allow for highly sensitive and time-resolved analysis of HBV-specific immune responses during acute and chronic infection.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2563
Author(s):  
Valeria Barili ◽  
Andrea Vecchi ◽  
Marzia Rossi ◽  
Ilaria Montali ◽  
Camilla Tiezzi ◽  
...  

In chronic hepatitis B and C virus infections persistently elevated antigen levels drive CD8+ T cells toward a peculiar differentiation state known as T cell exhaustion, which poses crucial constraints to antiviral immunity. Available evidence indicates that T cell exhaustion is associated with a series of metabolic and signaling deregulations and with a very peculiar epigenetic status which all together lead to reduced effector functions. A clear mechanistic network explaining how intracellular metabolic derangements, transcriptional and signaling alterations so far described are interconnected in a comprehensive and unified view of the T cell exhaustion differentiation profile is still lacking. Addressing this issue is of key importance for the development of innovative strategies to boost host immunity in order to achieve viral clearance. This review will discuss the current knowledge in HBV and HCV infections, addressing how innate immunity, metabolic derangements, extensive stress responses and altered epigenetic programs may be targeted to restore functionality and responsiveness of virus-specific CD8 T cells in the context of chronic virus infections.


2019 ◽  
Vol 128 ◽  
pp. 323-328 ◽  
Author(s):  
Hiva Mohammadizad ◽  
Mehdi Shahbazi ◽  
Mohammad Reza Hasanjani Roushan ◽  
Mehdi Soltanzadeh-Yamchi ◽  
Mousa Mohammadnia-Afrouzi

2001 ◽  
Vol 124 (3) ◽  
pp. 435-444 ◽  
Author(s):  
S. Matsumura ◽  
K. Yamamoto ◽  
N. Shimada ◽  
N. Okano ◽  
R. Okamoto ◽  
...  

1983 ◽  
Vol 4 (2) ◽  
pp. 100-102 ◽  
Author(s):  
Julie T. Jacobson ◽  
John P. Burke ◽  
Marlyn T. Conti

AbstractDuring a 30-month period in our 570-bed private community hospital, employees reported 218 injuries from needles and other sharp objects. Five of these injuries were from needles used on patients known to be hepatitis B surface antigens (HBsAg) positive. Four were from blades or scalpels used on HBsAg positive patients. A nother needle injury resulted in serious Staphylococcus aureus infection. Thirty-three percent of the injuries were from improperly disposed objects, generally in trash baskets in patient rooms. Housekeeping employees were the “innocent victims” of more than one-half of the injuries from such improperly disposed objects. A survey of reporting practices revealed housekeepers reported all their injuries. Underreporting was identified as a problem with laboratory personnel and nurses who tended to make their own judgment concerning the extent of the injury. An effective innovation resulting from our survey was the use of plastic irrigation bottles as an inexpensive and readily available container for disposal of sharps.


2016 ◽  
Vol 34 (4) ◽  
pp. 396-409 ◽  
Author(s):  
Katja Nitschke ◽  
Hendrik Luxenburger ◽  
Muthamia M. Kiraithe ◽  
Robert Thimme ◽  
Christoph Neumann-Haefelin

Approximately 500 million people are chronically infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) worldwide and are thus at high risk of progressive liver disease, leading to liver fibrosis, cirrhosis and ultimately hepatocellular cancer. Virus-specific CD8+ T-cells play a major role in viral clearance in >90% of adult patients who clear HBV and in approximately 30% of patients who clear HCV in acute infection. However, several mechanisms contribute to the failure of the adaptive CD8+ T-cell response in those patients who progress to chronic infection. These include viral mutations leading to escape from the CD8+ T-cell response as well as exhaustion and dysfunction of virus-specific CD8+ T-cells. Antiviral efficacy of the virus-specific CD8+ T-cell response also strongly depends on its restriction by specific human leukocyte antigens (HLA) class I alleles. Our review will summarize the role of HLA-A, B and C-restricted CD8+ T-cells in HBV and HCV infection. Due to the current lack of a comprehensive database of HBV- and HCV-specific CD8+ T-cell epitopes, we also provide a summary of the repertoire of currently well-described HBV- and HCV-specific CD8+ T-cell epitopes. A better understanding of the factors that contribute to the success or failure of virus-specific CD8+ T-cells may help to develop new therapeutic options for HBV eradication in patients with chronic HBV infection (therapeutic vaccination and/or immunomodulation) as well as a prophylactic vaccine against HCV infection.


2014 ◽  
Vol 60 (1) ◽  
pp. 136-145 ◽  
Author(s):  
Yinong Ye ◽  
Jing Liu ◽  
Qing Lai ◽  
Qiyi Zhao ◽  
Liang Peng ◽  
...  

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