Mutational escape from cellular immunity in viral hepatitis: variations on a theme

Alizei, Elahe Salimi; Hofmann, Maike; Thimme, Robert

doi:10.1016/j.coviro.2021.08.002

Cited by 12 publications

(6 citation statements)

References 61 publications

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“…Besides adaptation to the cellular system, the loss of T cell epitope could be due to immune escape, including adaptive immune escape. This has been shown in the case of chronic viral infection with LCMV, HCV, and HIV for CD8 T cells [ 60 ] and for CD4 T cells [ 61 ]. Chronic viral infection is a dynamic, metastable equilibrium process, whereas an acute viral infection is an out-of-equilibrium process.…”

Section: Testing the Hypothesesmentioning

confidence: 76%

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Pontarotti

Paganini²

2022

IJMS

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We propose a new hypothesis that explains the maintenance and evolution of MHC polymorphism. It is based on two phenomena: the constitution of the repertoire of naive T lymphocytes and the evolution of the pathogen and its impact on the immune memory of T lymphocytes. Concerning the latter, pathogen evolution will have a different impact on reinfection depending on the MHC allomorph. If a mutation occurs in a given region, in the case of MHC allotypes, which do not recognize the peptide in this region, the mutation will have no impact on the memory repertoire. In the case where the MHC allomorph binds to the ancestral peptides and not to the mutated peptide, that individual will have a higher chance of being reinfected. This difference in fitness will lead to a variation of the allele frequency in the next generation. Data from the SARS-CoV-2 pandemic already support a significant part of this hypothesis and following up on these data may enable it to be confirmed. This hypothesis could explain why some individuals after vaccination respond less well than others to variants and leads to predict the probability of reinfection after a first infection depending upon the variant and the HLA allomorph.

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Section: Testing the Hypothesesmentioning

confidence: 76%

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Pontarotti

Paganini²

2022

IJMS

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“…The mechanisms of this process are not well understood but a lack of CD4+ T cell help (see next section) is thought to play an important role. HCV is a rapidly mutating RNA virus and viral-escape from CD8+ T cell epitopes has been shown to be another key factor in the development of HCV persistence in chimpanzees and humans [ 123 ].…”

Section: Hepatic T Cell Subsets During Chronic Viral Hepatitismentioning

confidence: 99%

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

2023

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T cells play an important role in the clearance of hepatotropic viruses but may also cause liver injury and contribute to disease progression in chronic hepatitis B and C virus infections which affect millions of people worldwide. The liver provides a unique microenvironment of immunological tolerance and hepatic immune regulation can modulate the functional properties of T cell subsets and influence the outcome of a virus infection. Extensive research over the last years has advanced our understanding of hepatic conventional CD4+ and CD8+ T cells and unconventional T cell subsets and their functions in the liver environment during acute and chronic viral infections. The recent development of new small animal models and technological advances should further increase our knowledge of hepatic immunological mechanisms. Here we provide an overview of the existing models to study hepatic T cells and review the current knowledge about the distinct roles of heterogeneous T cell populations during acute and chronic viral hepatitis.

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“…In HCV and HIV infection, viral escape has been intensively studied [91,92] and recently reviewed in [93]. Three mechanisms that lead to an abrogated or diminished CD8+ T cell peptide recognition are known: amino acid changes in the region (i) of the binding pocket of HLA class I molecules, (ii) of the T cell receptor (TCR) interaction region [94], and (iii) flanking the epitope, leading to a failure of optimal epitope processing and presentation (Figure 1B) [92,95,96].…”

Section: Viral Escapementioning

confidence: 99%

Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection

Oberhardt

Hofmann

Thimme

2022

Viruses

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The hepatitis delta virus (HDV) is the smallest known human virus, yet it causes great harm to patients co-infected with hepatitis B virus (HBV). As a satellite virus of HBV, HDV requires the surface antigen of HBV (HBsAg) for sufficient viral packaging and spread. The special circumstance of co-infection, albeit only one partner depends on the other, raises many virological, immunological, and pathophysiological questions. In the last years, breakthroughs were made in understanding the adaptive immune response, in particular, virus-specific CD4+ and CD8+ T cells, in self-limited versus persistent HBV/HDV co-infection. Indeed, the mechanisms of CD8+ T cell failure in persistent HBV/HDV co-infection include viral escape and T cell exhaustion, and mimic those in other persistent human viral infections, such as hepatitis C virus (HCV), human immunodeficiency virus (HIV), and HBV mono-infection. However, compared to these larger viruses, the small HDV has perfectly adapted to evade recognition by CD8+ T cells restricted by common human leukocyte antigen (HLA) class I alleles. Furthermore, accelerated progression towards liver cirrhosis in persistent HBV/HDV co-infection was attributed to an increased immune-mediated pathology, either caused by innate pathways initiated by the interferon (IFN) system or triggered by misguided and dysfunctional T cells. These new insights into HDV-specific adaptive immunity will be discussed in this review and put into context with known well-described aspects in HBV, HCV, and HIV infections.

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Mutational escape from cellular immunity in viral hepatitis: variations on a theme

Cited by 12 publications

References 61 publications

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Studying T Cell Responses to Hepatotropic Viruses in the Liver Microenvironment

Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection

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