Persistence of the inuenza A/WSN/33 virus RNA at midbrain levels of immunodefective mice

Strains of inuenza A virus are known to infect speciŽc subpopulations of neurons in the mouse brain. Here we report that all segments of the genome of the neurotropic inuenza A virus, strain WSN/33, can persist in the brains of immunodefective transporter associated with Antigen Processing 1 (TAP1) mutant mice. Ten to 17 months after injection of virus into the olfactory bulbs, viral RNA encoding the nonstructural NS1 protein was detected in sections from the brain at midbrain levels by RT-PCR in almost all animals. Both negative-strand genomic RNA (vRNA) and positive-strand RNA, including mRNA, were found. RNA encoding nucleoprotein and polymerases, which form the replicative complex of the virus, were detected in fewer brains. RNA encoding envelope proteins were found only in occasional brains. No viral cDNA could be identiŽed. This observation shows that certain regions of the brain in immunodefective mice may harbor the genome of inuenza A virus including the NS1 gene, the products of which may play a regulatory role in host-cell metabolism. Journal of NeuroVirology (2001) 7, 117–124.