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Journal of Virology, October 2005, p. 12554-12565, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12554-12565.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Attenuated Rabies Virus Activates, while Pathogenic Rabies Virus Evades, the Host Innate Immune Responses in the Central Nervous System

Zhi W. Wang,1 Luciana Sarmento,1 Yuhuan Wang,2 Xia-qing Li,1 Vikas Dhingra,1 Tesfai Tseggai,1 Baoming Jiang,2 and Zhen F. Fu1,3*

Departments of Pathology,1 Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602,3 Centers for Disease Control and Prevention, Atlanta, Georgia 303332

Received 25 April 2005/ Accepted 1 July 2005

Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate the host responses to RV infection, we examined and compared the pathology, particularly the inflammatory responses, and the gene expression profiles in the brains of mice infected with wild-type (wt) virus silver-haired bat RV (SHBRV) or laboratory-adapted virus B2C, using a mouse genomic array (Affymetrix). Extensive inflammatory responses were observed in animals infected with the attenuated RV, but little or no inflammatory responses were found in mice infected with wt RV. Furthermore, attenuated RV induced the expression of the genes involved in the innate immune and antiviral responses, especially those related to the alpha/beta interferon (IFN-{alpha}/ß) signaling pathways and inflammatory chemokines. For the IFN-{alpha}/ß signaling pathways, many of the interferon regulatory genes, such as the signal transduction activation transducers and interferon regulatory factors, as well as the effector genes, for example, 2'-5'-oligoadenylate synthetase and myxovirus proteins, are highly induced in mice infected with attenuated RV. However, many of these genes were not up-regulated in mice infected with wt SHBRV. The data obtained by microarray analysis were confirmed by real-time PCR. Together, these data suggest that attenuated RV activates, while pathogenic RV evades, the host innate immune and antiviral responses.

* Corresponding author. Mailing address: Department of Pathology, College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Drive, Athens, GA 30602. Phone: (706) 542-7021. Fax: (706) 542-5828. E-mail: zhenfu{at}vet.uga.edu.

Journal of Virology, October 2005, p. 12554-12565, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12554-12565.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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