PATHOGENESIS OF NEUROVIRULENT INFLUENZA-A VIRUS-INFECTION IN MICE - ROUTE OF ENTRY OF VIRUS INTO BRAIN DETERMINES INFECTION OF DIFFERENT POPULATIONS OF CELLS

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 49  (6) , 686-692
Abstract
Coinfection of a cell culture with a human and avian influenza A virus yielded a recombinant virus with high neurovirulence for mice. The comparative pathogenesis of CNS infection in mice between the parental human and the recombinant virus was studied using the immunohistologic peroxidase-antiperoxidase method and virus assay of tissue suspensions. The human virus replicated poorly in mice and did not replicate in the brain even after intracerebral [i.c.] inoculation. The recombinant virus replicated to high titer in the lung and brain with resulting viremia after inoculation of young mice by the i.c., i.p., or intranasal [i.n.] routes. Different populations of cells in the brain became infected after inoculation by each of the 3 routes: choroid plexus, and ependymal and subependymal cells after i.c. inoculation cells in perivenous areas, neurons in the olfactory bulbs and trigeminal ganglia and nuclear groups in the brainstem and midbrain after i.n. inoculation. I.p. inoculation resulted almost exclusively in the perivenous spread of the virus. The i.n. inoculation suggested that virus entry into the brain by spread along nerve cell processes from the nasal mucosa to the brain and trigeminal ganglia and subsequent perivenous spread after viremia developed following virus replication in the lung. To dissect these 2 mechanisms neonatal mice that had acquired high levels of serum antibody by nursing from actively immunized mothers were inoculated. I.p. inoculation of these mice failed to cause infection; i.n. inoculation resulted in the same pattern of cellular spread through the olfactory and trigeminal pathways as noted previously. This proved that this recombinant influenza virus could invade the CNS after infection via a natural route of infection. This highly neuroinvasive agent provides 1 example of the extent of virulence which can be acquired by recombination of apathogenic influenza viruses and raises a note of caution for adequate control of those agents generated in the laboratory.