Invasion of brain by neurovirulent influenza A virus after intranasal inoculation

Abstract We examined the immunohistochemical localization of neurovirulent influenza A virus (WSN and R404BP) in the brains and lungs of C3H/HeN and A2G mice 3 days after intranasal inoculation, as well as in A2G mice 3 days after intracerebral inoculation. The invasion of brain by R404BP virus was greater than that of WSN in both mouse strains. The areas of infection were less extensive in Mx gene + A2G mice than in the Mx gene − C3H/HeN mice, which is consistent with previous reports. Major involvement was seen in various catecholaminergic neurons, capillaries, meninges and ependymal areas. Olfactory and trigeminal nerves were not positive for the WSN antigen. These results show that, in the early phase of infection, influenza A virus invades, probably through hematogenous spread, and particularly affects catecholaminergic neurons.