Selective Targeting of Habenular, Thalemic Midline and Monaminergic Neurons by Neurotropic Influenza A Virus

HABENULAR, THALAMIC MIDLINE AND MONOAMINERGIC NEURONS

Diehl, Ashok Chauhan, Hans-Gustaf Ljunggren, Krister Kristensson*

Depart. Neuroscience and MTC, Karolinska Institutet, Stockholm,

have been proposed to be associated with neuropsychiatric

complications, the mechanisms of which remain to be unraveled. 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. It the habenular and

paraventricular thalamic areas, infection was followed by an

almost total loss of neurons within 12 days. In the brainstem

monoaminergic areas, viral gene products were eliminated from

neurons by 12 days in B6 wildtype mice, but persisted 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 persist for a significant

period of time in specific regions of the brain in