Research Axis
Infectious Diseases and Acute Care Axis
Research Theme
Infection, immunity and inflammation
Address
CHUSJ - Centre de Recherche
Online
The long-term objectives of the laboratory are to characterize host-pathogen interactions and define novel therapies in the context of herpesviruses. These viruses can cause both mild and severe conditions in newborns, kids and adults. The laboratory work focuses on the intracellular transport route employed by herpes simplex virus type 1 (HSV-1), which are newly assembled in the nucleus, by identifying novel molecular players and characterizing their mechanisms of action. That transport is peculiar as herpesviral particles are too large to exit via the nuclear pores. Instead, they bud through the inner nuclear membrane to form enveloped perinuclear virions, which then fuse with the outer nuclear membrane to yield naked cytoplasmic capsids. Though highly unusual, that transport is not unique to herpesviruses as it was more recently discovered that large cellular hnRNP particles also use that pathway. This demonstrates, once again, that viruses are excellent models to study cellular processes.
Lab Findings
To study the intracellular transport of HSV-1 viral particles, the lab established a unique in vitro assay that reconstitutes nuclear egress, which enabled it to confirm the aforementioned egress model. That assay, coupled with mass spectrometry, also led to the identification of novel host and viral proteins onto the nuclear capsids, which the lab is now characterizing. Since the way by which the virus escapes the nuclei lacks molecular details, the lab further explores the role of the viral glycoprotein M (gM). That protein is quickly and specifically targeted to the nuclear membranes before the virus leaves the nucleus, but its role there is unknown. Most interestingly, it interacts with several proteins that regulate viral fusion and which the lab is probing. Another critical step is the acquisition of the final viral enveloped. Based on work by the Lippé and other labs, the virus travels through the TGN before reaching the cell surface, a process that is dependant on the host protein kinase D. Recent work, however, hinted at an elaborate scenario whereby PKD effector play multiple roles along the viral egress pathway, so more research is required.
HSV-1 has a complex life cycle whose molecular details needs clarification. One aspect is the overall contribution of the cell to the propagation of the virus. To grasp this significant aspect, a proteomics program was put in place. Aside from the above findings, this program revealed the presence of 49 host proteins in mature HSV-1 virions. Current efforts are to understand their functions in the virus. Finally, the lab established a highly innovative flow virometry approach to characterize individual viral particles by cytometry and even purify viral particles. This enables the lab to study various viral intermediates.
Career Summary
Dr. Lippé completed his training in cell biology and virology at the Universities of Montreal (BSc), McMaster (MSc) and British Columbia (PhD) and finally via a postdoc at the European Molecular Biology Laboratories (EMBL) in Germany. He then establishes his lab in 2001 in the Department of Pathology and cell biology at the University of Montreal initially as an adjunct professor. He later became associate professor then full professor. In 2019, he joined the new CHU Sainte-Justine Research Center where he continues to pursue his research while maintaining his affiliations with the University of Montreal.
Laboratory
Dr Roger Lippé Laboratory