Transcriptional Arrays Of Mouse Brain Induced By Fixed And Street Rabies Viruses Strain Infection

Rabies is a highly contagious lethal zoonosis caused by rabies virus, which is characterized as neurotropic infection,its pathogenesis remains unclear。Although significant clinical manifestations could be produced on the cases infected by street strain, significant pathological changes hardly be detected.This work attempt to explore the relationships between the neurological dysfuction mechanizms and the transcription levels of genes in brain tissues or cultured primary neurons infected by the fixed and street rabies viruses.BALB/C mice were intracerebrally infected by a fixed strain CVS and street strain PB4 respectively, the infected brains were collected at 96 h and 144 h. The total RNAs were extracted, the differentially expressed genes were screened on Affymetrix mouse genome oligonucleotide microarrays. The data showed that more differentially expressed genes were demonstrated in CVS infected tissues than the PB4s. Some upregulated or downregulated genes which might imply to the dysfunction of central nervous system were choozen and confirmed by real-time PCR. The gene functions involved in the immune and antiviral responses, such as Ccl5, Cxcl10, Ifit1 and Ifi27/2a, etc, were highly stimulated in CVS infected brain tissues,The gene related to neurotransmitter receptors, as Grbra3 and Grm3, were up-regulated in the 96h tissues of either strains, however, TH and Pmch genes were down-regulated at 96 h and 144 h tissues, respectively.Furthermore, primary mouse cortical neurons were prepared and infected by the two strains. Both of them could improve the levels of genes pointed to immune and antiviral responses.Due to the roles of rabies virus glycoprotein(G) in pathogenicity, the recombinant plasmids related to the G gene of CVS and PB4 strains were construtcted, and the primers and Taqman probes were also designed, the results revealed that G gene copies were far lower in brains infected by PB4 than CVS,however, no differences were presented in cultured primary neurons infected by either strain.All these may be useful in rabies virus pathogenesis elucidation.