Project description
Appearance of adaptative mutations within viral genomes allowed their proteins to slowly get the capability to interfere with and modulate cellular processes to favour their own replication and for many viruses to establish a chronic infection. This ability to manipulate the host is even more remarkable with viruses that produce a very limited set of proteins. In this regard, the hepatitis B virus (HBV), which encodes only 7 proteins, can replicate in the human liver indefinitely. To succeed, HBV needs not only to balance its intrahepatic replication level perfectly but also to dampen the immune system. To achieve this, HBV produces 3 envelope proteins (HBsAg-L, HBsAg-M and HBsAg-S) that are key factors for both the production of Dane particles (infectious virions) and non-infectious subviral particles (SVPs) that lead to the exhaustion of the immune system. Therefore, understanding the maturation of these proteins and how they are trafficking within the cells to balance the production of the different types of viral particles should reveal virus-host interactions that are mechanistically important for the virus to get control of the host.
Within the scientific community, there is currently no consensus on how the HBV envelope proteins mature and assemble to form the different forms of HBV particles. Therefore, the long-term goal of this research program is to define the spatiotemporal events leading to the maturation of the various forms of HBV particles. As a first step toward this goal, we took a proteomic approach to identify host factors involved in the HBsAg synthesis. Our findings show that the J-protein chaperones DNAJB12 and DNAJB14 are essential for infectious HBV particles secretion. Therefore, the recruited phD student will use our knowledge on DNAJB12 to develop a spatiotemporal map of protein-protein interactions occurring between the HBsAg and the surrounding host factor during viral egress. To do so, we will use a very innovative proteomic technique, called Proximity Labeling. More specifically, the TurboID and the split-TurboID biotin ligases will be used to tag, in live HBV replicating cells, all proteins in the microenvironment of a targeted protein (here DNAJB12 or L-HBsAg).
Start date
as soon as possible
Research supervision
Patrick Labonté, professor
Location
Armand-Frappier Santé Biotechnologie Research Centre
531 des Prairies Blvd.
Laval, Quebec H7V 1B7
How to apply
Candidates interested should email their application to patrick.labonte@inrs.ca with (1) their resume; (2) a cover letter; (3) their academic transcripts; (4) the contact information of two references.
Questions
Patrick Labonté, professor
patrick.labonte@inrs.ca