HIPShot · HBV GenetIc and Proteomic Screen
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-03-04 → 2021-03-03
- EU contribution
- €185,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
HBV GenetIc and Proteomic Screen
Viral infections pose a constant threat to human societies by causing substantial morbidity and mortality worldwide. Over 500 million people worldwide, are still persistently infected with hepatitis B virus (HBV), hepatitis delta virus (HDV), and/or HCV. In fact, these viruses constitute many challenges to the medical community worldwide for several reasons. First, they specifically infect the liver, a vital detoxifying organ whose damage can have important consequences on patients’ lives. Second, no satisfactory treatment options are always available against these viruses. Third, the outcome of HBV, HCV or HBV/HDV persistent infections often manifests in a sequential progression from chronic liver disease, to fibrosis, then cirrhosis, culminating in hepatocellular carcinoma (HCC). Finally, the challenges these viruses pose are largely due to our inability to target them due to our lack of knowledge on fundamental aspects of their lifecycles. HIPSHOT aimed in gaining insights into the mechanisms by which HBV and HDV viral genomes exploit their host environment to promote their replication and persistence. By doing so, HIPSHOT not only revealed unforeseen biological knowledge, but also yielded new targets for host-directed antiviral therapies to combat infection and chronic inflammation. The overall objective of this project was to discover and understand how HBV and HDV are able to infect and replicate in human hepatocytes through interactions with cellular host factors.The objective was reached through the following specific aims: 1. Comprehensive identification of proteins associated with the HBV and HDV genomes. 2. Uncovering pro- or anti-viral factors through genetics screens and dissecting their roles in viral replication. In conclusion, through proteomics and genetic approaches, I was able to identify a list of genes associated with HBV and HDV infections. These genes encode hepatic host factors important during the course of viral replication, playing either pro-viral or antiviral roles. The identified host factors would help answering unresolved questions concerning HBV and HDV lifecycles (e.g. cccDNA formation, HDV sensing). Most importantly the identified factors constitute ideal drug targets, suitable for the development of novel antiviral therapies against these viruses.
Data: CORDIS, © European Union
Project objective
Hepatitis B virus (HBV) is a major global health problem resulting in progressive liver disease, including cirrhosis and hepatocellular carcinoma – the second leading cause of cancer death worldwide. Although HBV structure and genome have been characterized, key aspects of the viral life cycle remain poorly understood because of the lack of a robust HBV infectious tissue culture system. Moreover, despite the development of a safe and efficient vaccine, over 240 million people are chronically infected with HBV. Thus, the development of efficient anti-viral strategies to cure HBV infection remains a critical unmet medical need. To date, there is an important gap of knowledge in basic HBV biology that results in the lack of identified drug targets to cure chronic HBV infection. These limitations can now be overcome using a state-of-the-art HBV tissue culture model combined with technological advances in genetics and proteomics. The aim of HIPShot (Hbv genetIc and Proteomic Screen) is to use cutting-edge screening techniques in human cells to identify host factors that are essential for HBV infection and at the same time targets for antiviral cure. With my expertise in using forward genetic screening and proteomic approaches, I decided to join one of the leading groups in HBV research, lead by Prof. Thomas Baumert (TB) and based at Inserm Unit U1110 of Université de Strasbourg (UdS), to exploit novel technologies in the investigation of host-virus interaction. The proposed project will provide unmatched insights into the basic biology of HBV infection by shedding new light on cellular host factors exploited by HBV to replicate and persist in human cells. These identified host factors will constitute direct drug targets with an important therapeutic potential.
Original text from CORDIS.
Participants
- UNIVERSITE DE STRASBOURG · StrasbourgCoordinatorFrance
Links
Data: CORDIS, © European Union