Hepatitis Delta Virus Acts as an Immunogenic Adjuvant in Hepatitis B Virus-Infected Hepatocytes

Autor: Anthony T. Tan, Tassilo Volz, Maura Dandri, J Kah, Marta Borghi, Yvonne Ladiges, Antonio Bertoletti, Marc Lütgehetmann, Pietro Lampertico, Adeline Chia, Camille Sureau, Christine Y.L. Tham, Alessandro Loglio, Katja Giersch
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
RNA viruses
medicine.medical_treatment
viruses
Mice
SCID
medicine.disease_cause
Chronic liver disease
Virus Replication
human liver chimeric mice
Mice
Medicine
Immunogenetic Phenomena
lcsh:R5-920
Antigen processing
viroid
Coinfection
virus diseases
Hep G2 Cells
Middle Aged
Hepatitis B
Chemotherapy
Adjuvant
Female
immunotherapy
Hepatitis Delta Virus
Viral hepatitis
lcsh:Medicine (General)
Adult
CAR-T cell therapy
Hepatitis B virus
Antigen presentation
Primary Cell Culture
viral hepatitis
General Biochemistry
Genetics and Molecular Biology
Virus
Article
Cell Line
Immune system
Animals
Humans
Aged
business.industry
chronic liver disease
Immunotherapy
Interferon-beta
biochemical phenomena
metabolism
and nutrition
medicine.disease
Virology
Immunity
Innate
digestive system diseases
Disease Models
Animal
Hepatocytes
business
Zdroj: Cell Reports Medicine, Vol 1, Iss 4, Pp 100060-(2020)
Cell Reports Medicine
ISSN: 2666-3791
Popis: Summary Hepatitis delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes severe hepatitis, with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we study the impact of HDV on viral antigen processing and presentation. Using in vitro models of HBV/HDV co-infection, we demonstrate that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV-infected cells through the upregulation of the antigen processing pathway mediated by IFN-β/λ. Liver biopsies of HBV/HDV patients confirm this upregulation. We then validate in vitro and in a HBV/HDV preclinical mouse model that HDV infection increases the anti-HBV efficacy of T cells with engineered T cell receptors. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and advocate the utilization of engineered HBV-specific T cells as a potential treatment for HBV/HDV co-infection.
Graphical Abstract
Highlights HDV infection affects viral antigen processing and presentation HDV boosts HBV epitope presentation on HBV/HDV and mono-HBV-infected hepatocytes Anti-HBV efficacy of T cells engineered with T cell receptors is enhanced by HDV
Tham et al. demonstrate that HDV activates hepatocyte antigen processing and presentation capacity, increasing their activation of virus-specific T cells. HDV, a defective RNA virus that relies on HBV envelope proteins to infect hepatocytes, exacerbates HBV-related liver pathology. This immunological adjuvant-like feature can increase the anti-HBV efficacy of immunological therapy.
Databáze: OpenAIRE
Externí odkaz: