Attenuated rabies virus activates, while pathogenic rabies virus evades, the host innate immune responses in the central nervous system.
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/beta) signaling pathways and inflammatory chemokines. For the IFN-alpha/beta 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.
Wang
Zhi W
ZW
Department of Pathology, College of Veterinary Medicine, University of Georgia, 501 D.W. Brooks Drive, Athens, GA 30602, USA.
Sarmento
Luciana
L
Wang
Yuhuan
Y
Li
Xia-qing
XQ
Dhingra
Vikas
V
Tseggai
Tesfai
T
Jiang
Baoming
B
Fu
Zhen F
ZF
D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018925:Chemokines / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000378:metabolism; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D011818:Rabies / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011820:Rabies virus / Q000276:immunology* / Q000472:pathogenicity*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D014774:Virulence
D000956:Antigens, Viral; D018925:Chemokines; D004268:DNA-Binding Proteins; D006023:Glycoproteins; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus; D007372:Interferons