Hepatitis B virus (HBV) infection is a major global health problem, resulting in progressive liver disease, including cirrhosis and hepatocellular carcinoma. While current therapies control infection, viral cure is rarely achieved. Using a liver cell-based system of HBV infection combined with single cell profiling, we aim to unravel the host cell responses to hepatitis B virus infection in individual cells enabling to discover key drivers of transcriptional reprogramming by the virus. More specifically, leveraging spatial and temporal profiling, we aim to obtain a comprehensive overview of the impact of the virus on the transcriptomic patterns of hepatocytes, including host responses to viral infection and modulation of host factors involved required for the HBV life cycle and immune evasion. Using state-of-the-art techniques for the integrative analysis of single cell and time course gene expression profiles, we expect to emerge with several discrete host targets that represent candidates for the design of small molecule therapeutics for cure of infection. We hypothesize that our integrative analysis will allow us to decipher unexplored virus-host interactions of particular interest for the development of viral curative strategies.

Public Health Relevance

The goal of this project is to unravel the host cell responses to hepatitis B virus infection using spatial and temporal profiling on the single cell level. Integrative analysis of spatial and temporal gene expression profiles will enable to discover key drivers of transcriptional reprogramming by the virus, opening the way to targeted drug discovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI131066-02
Application #
9618850
Study Section
Virology - B Study Section (VIRB)
Program Officer
Koshy, Rajen
Project Start
2018-01-01
Project End
2020-12-31
Budget Start
2019-01-01
Budget End
2020-12-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Verrier, Eloi R; Yim, Seung-Ae; Heydmann, Laura et al. (2018) Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase Sensing in Human Hepatocytes. Hepatology 68:1695-1709
Ligat, Gaetan; Schuster, Catherine; Baumert, Thomas F (2018) HBV core variants, liver fibrosis and hepatocellular carcinoma. Hepatology :
Champion, Magali; Brennan, Kevin; Croonenborghs, Tom et al. (2018) Module Analysis Captures Pancancer Genetically and Epigenetically Deregulated Cancer Driver Genes for Smoking and Antiviral Response. EBioMedicine 27:156-166
Foung, Steven K H; Baumert, Thomas F (2018) Editorial: Current Progress and Challenges in the Development of a B Cell Based Hepatitis C Virus Vaccine. Front Immunol 9:2577