Expression of the ACE2 virus entry protein in the nervus terminalis suggests an alternative route for brain infection in COVID-19.
Previous studies suggested that the SARS-CoV-2 virus may gain access to the brain by using a route along the olfactory nerve. However, there is a general consensus that the obligatory virus entry receptor, angiotensin converting enzyme 2 (ACE2), is not expressed in olfactory receptor neurons, and the timing of arrival of the virus in brain targets is inconsistent with a neuronal transfer along olfactory projections. We determined whether nervus terminalis neurons and their peripheral and central projections may provide an alternative route from the nose to the brain. Nervus terminalis neurons were double-labeled with antibodies against ACE2 and nervus terminalis markers in postnatal mice. We show that most nervus terminalis neurons with cell bodies in the region between the olfactory epithelium and the olfactory bulb express ACE2, and therefore may provide a direct route for the virus from the nasal epithelium and Bowman's glands to brain targets, including the telencephalon and diencephalon.
Christopher S von Bartheld, Katarzyna Bilinska, Rafal Butowt
bioRxiv : the preprint server for biology