Respiratory viruses and nasal cavity

The nasal cavity is the first area infected by many respiratory viruses, including influenza, respiratory syncytial, and SARS-CoV-2. This primary infection is of major interest because it precedes the infection of the lungs leading to respiratory distress. In addition, the nasal cavity serves as a reservoir for the virus to be transmitted by aerosols. In addition, respiratory viruses can cross the blood-brain barrier to infect the central nervous system through infection of the olfactory neurons, located in the olfactory mucosa. In fact, by infecting these neurons in direct contact with the environment, they can travel up their axons to enter the olfactory bulb, the first relay for olfactory information in the central nervous system. This path is called the "olfactory pathway". Beyond these aspects of virus propagation, the nasal cavity can also be affected in its function leading to loss of smell linked to viral infections.

The projects we are developing aim to better understand:

• The defenses present in the nasal cavity, in particular at the level of the olfactory mucosa to limit the passage of respiratory viruses through the olfactory rail.

• The impact of respiratory viruses on the nasal cavity, in particular to explain anosmia (loss of smell) highlighted in particular during the COVID-19 epidemic where the prevalence of odor disorders reaches nearly 50% of patients for the early variant of concerns.

We are mainly studying SARS-CoV-2 infection on the hamster model. In this case the virus does not enter the olfactory bulb because its infection is mainly limited to the supporting cells of the olfactory epithelium (sustentacular cells).

In addition, these infections result in massive damage of the olfactory epithelium leading to desquamation associated with infiltration of immunecells (EO Olfactory Epithelium / LP Lamina Propria; the white asterisk shows an area of desquamation in the lumen of the nasal cavity). We have shown that this damage are arising mainly from neutrophil activity (revealed by MPO staining below).

We are now exploring the early signals between the infected epithelium and immune cells leading to the damage of the infected epithelia.