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2005 Georgia Veterinary Scholars

Georgia Veterinary Scholar	Faculty Mentor
Heather Sheppard University of Georgia Class of 2008	Dr. Zhen Fu

Attenuated rabies virus induced more expression of chemokines in the CNS of mice than pathogenic rabies virus as detected by real time-PCR

Heather Sheppard 1*, ZhiWei Wang 1, Yi Kuang 1, Zhen F. Fu 1,2,

Departments of Pathology 1 and Infectious Diseases 2, College of Veterinary Medicine, University of Georgia

Rabies remains a public health threat worldwide, but the mechanisms leading to death are still unknown. Previous studies in our laboratory using functional genomics have indicated that attenuated rabies virus (RV) activates, while pathogenic RV evades, the host innate immune responses, particularly the IFN- a/b pathway and chemokines. To confirm the expression of chemokine genes in RV-infected mice, real time-PCR was used in this study. Mice were infected with pathogenic wildtype silver-haired bat RV (SHBRV) or attenuated RV strains SN-10 and B2C by either the intracerebral or intramuscular routes. At the time of paralysis, mice were euthanized and brains harvested for RNA extraction. Primers specific for 9 chemokines (ccl2, ccl3, ccl4, ccl5, ccl7, ccl11, cxcl9, cxcl10, cxcl11) and the house-keeping gene GAPDH were used for real time-PCR. It was found that the expression of most of these chemokines was at least 2 to 4 fold higher in mice infected with attenuated RV than pathogenic RV in both IC and IM infections. In IM infection with B2C, ccl2, ccl3, ccl4, ccl5, cxcl9, cxcl10, cxcl11, were upregulated. Similarly, in IC infection with B2C ccl5, ccl7, cxcl9, cxcl10, and cxcl11 were upregulated, while in IC infection with SN-10 ccl3, ccl4, ccl5,ccl7, cxcl9, cxcl10, and cxcl11 were also upregulated in comparison to the pathogenic wildtype strain. These data confirm previous observations by DNA microarray. Attenuated RV induced more expression of chemokins than pathogenic RV. Together, these data suggest that induction of innate immune responses is an important mechanism of RV attenuation.