Abstract:
Objective Rabies is a highly lethal zoonotic infectious disease caused by rabies virus (RABV). Type I interferon (IFN-I) pathway plays an important role in resisting RABV infection. RABV can escape the antiviral effect of IFN-I through the function of its phosphoprotein and nucleoprotein. The aim of the study was to investigate the role of glycoprotein (G), which has an important impact on the pathogenicity of RABV, in regulating IFN-I pathway needs more comprehensive exploration.
Method This study replaced the G gene of the RABV attenuated strain Hep-Flury with the G gene of the pathogenic strain CVS-11 to rescue and acquire the recombinant virus HepG. We analyzed the differences in the activation and regulation of IFN-I pathway in vivo and in vitro infected with Hep-Flury, CVS-11 and HepG, and compared the differences of these virus strains in fighting against antiviral effect of IFN-I in nerve cells.
Result After replacing G gene, the recombinant virus HepG had enhanced pathogenicity, was able to kill 100% of mice and the proliferation level in the mouse brain was significantly higher than that of the parental strain Hep-Flury. While infecting mouse brain early and in vitro neuronal cells, the attenuated strain Hep-Flury was able to activate the expression of IFN-I pathway-related genes faster, and the activation ability of HepG was between that of Hep-Flury and CVS-11. After activation of the IFN-I pathway in neuronal cells using Poly(I:C), the proliferation of Hep-Flury was significantly inhibited, and the replication of CVS-11 and HepG was almost unaffected, showing some resistance.
Conclusion G protein of RABV plays an important role in regulating and resisting the IFN-I pathway, providing the clue and evidence for further exploring how the G protein of RABV pathogenic strains helps the virus escape IFN-I pathway in the central nervous system.
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