Download The olfactory nerve: A shortcut for influenza viruses into the CNS

The olfactory nerve: A shortcut for influenza viruses into the CNS?
Debby van Riel, Lonneke Leijten, Ab Osterhaus and Thijs Kuiken
Department of Viroscience, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The
Netherlands
Research question and background
Influenza virus infections cause primarily respiratory disease in humans, with central
nervous system (CNS) disease as the most common extra-respiratory complication. The
pathogenesis of influenza virus induced CNS disease and the mechanism how influenza
viruses enter the CNS is poorly understood. Our research focuses on the olfactory
nerve, which directly connects the nasal cavity with the CNS, as a route of entrance into
the CNS. The main cell type of the olfactory nerve is the olfactory receptor neuron
(ORN) which has a dendrite that reaches into the nasal cavity and an axon that extends
into the olfactory bulb, which is part of the CNS. Previously, we have shown in ferrets
that influenza virus is able to enter the CNS via the olfactory nerve by infection of ORNs
(Schrauwen 2012). However, the permissiveness of human ORNs for influenza virus
infection has never been studied. Therefore, we want to study the interaction of human
olfactory receptor neurons with influenza viruses, using attachment studies and primary
olfactory receptor neuron cultures.
Methods and tissues used
To determine the attachment of different influenza virus subtypes by virus histochemistry
we collected formalin-fixed paraffin-embedded normal human olfactory mucosa. In
addition, we want to set up a primary ORN culture, using human olfactory mucosa as a
starting material, to study the interaction between these cells and influenza viruses in an
in vitro system.
Results and conclusion
So far, we have obtained two normal human olfactory mucosa tissues in formalin.
Preliminary attachment studies have shown that different influenza virus subtypes are
able to attach to the apical side of the olfactory mucosa. Since attachment is the first
step in the influenza virus replication cycle this is the first indication that in humans
influenza viruses could infect ORNs and subsequently spread to the CNS.