Intracellular transport of herpes simplex virus type 1 (HSV-1) capsids

 

Herpes viruses are wide spread pathogens that afflict most humans and are associated with several benign conditions (e.g. cold sores, mononucleosis, varicella, etc) but also sexually transmitted diseases, zona, potentially severe congenital conditions and even virus-induced blindness. Once infected, these viruses remain dormant in our body and can periodically reactivate.

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A major objective of the laboratory has been to characterize the molecular interactions of herpes simplex virus type 1 (HSV-1) with its host cells. This virus, as all members of the herpes family, replicates its genome and incorporates it into newly assembled viral capsids in the nucleus. These voluminous particles then escape the nucleus by an unusual route, since too big to traverse the nuclear pores. This involves the budding of the capsids through the inner nuclear membrane, yielding enveloped short-lived perinuclear viral particles. These particles then fuse with the outer nuclear membrane to release naked capsids in the cytoplasm. Another critical step in the egress of the newly produced viral particles is their acquisition of a final and mature envelope from an intracellular compartment, from which it finally reaches the cell surface. While this replication life cycle is generally accepted, the molecular machinery driving these processes are poorly understood (see the HSV-1 replication model below).  

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To study the complex exit of herpesviruses, our lab employs a combination of classical cell biology, biochemistry and virology tools as well as innovative technologies such as mass spectrometry, flow virometry and in vitro assays to address HSV-1 viral egress.  This has enabled us to define the total protein composition of mature and intermediates viral particles, reveal the incorporation of many cellular particles in those particles and characterize so far the functions of some of them. This should pave the way to novel therapeutic treatments by targeting cellular proteins that are essential for these viruses.

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Coronaviruses

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COVID-19 has had a tremendous impact on our society and the health of people. We therefore harnessed our expertise in virology and host-pathogen interactions to probe and characterize by innovative means the cellular proteins incorporated into mature coronaviruses. This will enable us to better to decipher their host-interactions and ultimately design novel therapeutics.

 

 

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Alzheimer's disease research

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We recently unveiled molecular links between HSV-1 and Alzheimer. We are now exploring whether the virus alters the formation of amyloid plaques and may contribute to the disease.