Ethanol attenuates presentation of cytotoxic T‐lymphocyte epitopes on hepatocytes of HBV‐infected humanized mice Article Swipe
Murali Ganesan
,
Weimin Wang
,
Saumi Mathews
,
Edward Makarov
,
Moses New‐Aaron
,
Raghubendra Singh Dagur
,
Antje Malo
,
Ulrike Protzer
,
Kusum K. Kharbanda
,
Carol A. Casey
,
Larisa Y. Poluektova
,
Natalia A. Osna
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1111/acer.14740
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1111/acer.14740
Background and Aims Approximately 3.5% of the global population is chronically infected with Hepatitis B Virus (HBV), which puts them at high risk of end‐stage liver disease, with the risk of persistent infection potentiated by alcohol consumption. However, the mechanisms underlying the effects of alcohol on HBV persistence remain unclear. Here, we aimed to establish in vivo / ex vivo evidence that alcohol suppresses HBV peptides‐major histocompatibility complex (MHC) class I antigen display on primary human hepatocytes (PHH), which diminishes the recognition and clearance of HBV‐infected hepatocytes by cytotoxic T‐lymphocytes (CTLs). Methods We used fumarylacetoacetate hydrolase (Fah)‐/‐, Rag2‐/‐, common cytokine receptor gamma chain knock‐out (FRG‐KO) humanized mice transplanted with human leukocyte antigen‐A2 (HLA‐A2)‐positive hepatocytes. The mice were HBV‐infected and fed control and alcohol diets. Isolated hepatocytes were exposed ex vivo to HBV 18‐27‐HLA‐A2‐restricted CTLs to quantify cytotoxicity. For mechanistic studies, we measured proteasome activities, unfolded protein response (UPR), and endoplasmic reticulum (ER) stress in hepatocytes from HBV‐infected humanized mouse livers. Results and Conclusions We found that alcohol feeding attenuated HBV core 18‐27‐HLA‐A2 complex presentation on infected hepatocytes due to the suppression of proteasome function and ER stress induction, which diminished both the processing of HBV peptides and trafficking of HBV‐MHC class I complexes to the hepatocyte surface. This alcohol‐mediated decrease in MHC class I‐restricted antigen presentation of the CTL epitope on target hepatocytes reduced the CTL‐specific elimination of infected cells, potentially leading to HBV‐infection persistence, which promotes end‐stage liver disease outcomes.
Related Topics
Concepts
Cytotoxic T cell
CTL*
Hepatitis B virus
MHC class I
Immunology
Biology
Humanized mouse
Epitope
Antigen presentation
Major histocompatibility complex
Ex vivo
Antigen
Virology
CD8
Immune system
T cell
In vivo
Virus
In vitro
Biochemistry
Biotechnology
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1111/acer.14740
- OA Status
- green
- Cited By
- 7
- References
- 46
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3212953733
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3212953733Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1111/acer.14740Digital Object Identifier
- Title
-
Ethanol attenuates presentation of cytotoxic T‐lymphocyte epitopes on hepatocytes of HBV‐infected humanized miceWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-11-13Full publication date if available
- Authors
-
Murali Ganesan, Weimin Wang, Saumi Mathews, Edward Makarov, Moses New‐Aaron, Raghubendra Singh Dagur, Antje Malo, Ulrike Protzer, Kusum K. Kharbanda, Carol A. Casey, Larisa Y. Poluektova, Natalia A. OsnaList of authors in order
- Landing page
-
https://doi.org/10.1111/acer.14740Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.ncbi.nlm.nih.gov/pmc/articles/8799491Direct OA link when available
- Concepts
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Cytotoxic T cell, CTL*, Hepatitis B virus, MHC class I, Immunology, Biology, Humanized mouse, Epitope, Antigen presentation, Major histocompatibility complex, Ex vivo, Antigen, Virology, CD8, Immune system, T cell, In vivo, Virus, In vitro, Biochemistry, BiotechnologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
7Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2, 2024: 1, 2023: 1, 2022: 3Per-year citation counts (last 5 years)
- References (count)
-
46Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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