Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection
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-inf...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/2/198 |
| _version_ | 1797476090738900992 |
|---|---|
| author | Valerie Oberhardt Maike Hofmann Robert Thimme Christoph Neumann-Haefelin |
| author_facet | Valerie Oberhardt Maike Hofmann Robert Thimme Christoph Neumann-Haefelin |
| author_sort | Valerie Oberhardt |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:53:03Z |
| format | Article |
| id | doaj.art-e94b9705375b473e8ba1f06b7dc434b1 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T20:53:03Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-e94b9705375b473e8ba1f06b7dc434b12023-11-23T22:29:04ZengMDPI AGViruses1999-49152022-01-0114219810.3390/v14020198Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV InfectionValerie Oberhardt0Maike Hofmann1Robert Thimme2Christoph Neumann-Haefelin3Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79110 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79110 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79110 Freiburg, GermanyDepartment of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, 79110 Freiburg, GermanyThe 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.https://www.mdpi.com/1999-4915/14/2/198hepatitis D virus (HDV)viral escapeCD8+ T cellsCD4+ T cellsT-cell exhaustionimmune-mediated pathogenesis |
| spellingShingle | Valerie Oberhardt Maike Hofmann Robert Thimme Christoph Neumann-Haefelin Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection Viruses hepatitis D virus (HDV) viral escape CD8+ T cells CD4+ T cells T-cell exhaustion immune-mediated pathogenesis |
| title | Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection |
| title_full | Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection |
| title_fullStr | Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection |
| title_full_unstemmed | Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection |
| title_short | Adaptive Immune Responses, Immune Escape and Immune-Mediated Pathogenesis during HDV Infection |
| title_sort | adaptive immune responses immune escape and immune mediated pathogenesis during hdv infection |
| topic | hepatitis D virus (HDV) viral escape CD8+ T cells CD4+ T cells T-cell exhaustion immune-mediated pathogenesis |
| url | https://www.mdpi.com/1999-4915/14/2/198 |
| work_keys_str_mv | AT valerieoberhardt adaptiveimmuneresponsesimmuneescapeandimmunemediatedpathogenesisduringhdvinfection AT maikehofmann adaptiveimmuneresponsesimmuneescapeandimmunemediatedpathogenesisduringhdvinfection AT robertthimme adaptiveimmuneresponsesimmuneescapeandimmunemediatedpathogenesisduringhdvinfection AT christophneumannhaefelin adaptiveimmuneresponsesimmuneescapeandimmunemediatedpathogenesisduringhdvinfection |