Screening of upregulated genes in suckling mouse central nervous system during the disease stage of rabies virus infection.

The pathogenesis of hydrophobia remains unclear. The aim of this study was to identify the differentially upregulated genes that correlated with disease development in an experimental mouse model to provide better understanding of pathological mechanisms in rabies. The present work employed Clontech mouse array 1.2 II containing 1,176 gene transcripts. Suckling mice were intracerebrally infected with canine rabies virus. The gene expression profiles on day 2, 4 and 6 post inoculation were followed. The results show genes whose expression increased at least twofold above the control, mock-infected brain. The numbers of genes showing altered expression level were 29, 109 and 98 genes on day 2, 4 and 6, respectively. The genes with altered expression were classified into eight major groups, namely immune response, metabolism, receptor and transporter, growth factors, death mediated factors, transcription and translation factors, proteases, and kinases. The numbers of upregulated genes during the disease stage was much higher than during the asymptomatic stage. This suggested that direct interaction between RABV and target cells induced massive destruction of a cellular homeostasis which may lead to functional termination of the CNS.