Selective targeting of habenular, thalamic midline and monoaminergic brainstem neurons by neurotropic influenza A virus in mice

Infections caused by influenza A virus have been proposed to be associated with neuropsychiatric complications, the mechanisms of which remain to be unravelled. We here report that a neurotropic strain of influenza A virus (A/WSN/33) introduced into the olfactory bulbs of C57BL/6 (B6) mice, selectively attacks habenular, paraventricular thalamic, and brainstem monoaminergic neurons. In the habenular and paraventricular thalamic areas, infection was followed by an almost total loss of neurons within 12 days. In the brain stem monoaminergic areas, viral gene products were eliminated from neurons by 12 days in B6 wildtype mice, but remained for at least 35 days in immunodefective TAP1 (Transporter associated with Antigen Presentation 1) mutant mice. In conclusion, we show that influenza A virus infection in the brain selectively targets regions which have been implicated in neuropsychiatric disturbances, and that this virus can remain for a significant period of time in specific regions of the brain in immunodefective mice.