Establishment Of The Dog Model With Rabies Virus Street Strain DRV-SX-09

Rabies is an acute zoonotic disease with high fatality, caused by rabies virus (RABV). RABV infects the central nervous system. There are classic furious rabies and paralytic rabies. The furious rabies is the most common type. The typical clinical symptoms of the furious rabies include excessive salivation, hydrophobia and agressiveness. Almost all the warm-blooded animals can be infected by RABV. Once clinical symptoms appear, the mortality rates are as high as100%. Rabies remains a major threat to public health around the world. It not only causes more than60,000human deaths each year, but also causes the seriousness of economic loss in the world.Pre-exposure and post-exposure prophylaxis (PEP) is the main measure for the prevention and control of rabies. However, in recent years, because of the mismanagement of domestic dogs or the invasion of stray dogs and wild animals, the epidemics of rabies are emerging again. However, the pathogenesis of rabies is still not clear. There are only few scientific studies on the canine model of rabies, which seriously restricts the investigation of rabies pathogenesis and the development of novel vaccines. So it is imperative to establish a standardized, reliable and repeatable rabies infection model in dogs.In this present study, the street rabies strain DRV-SX-09was inoculated into the temporal and masseter muscles of6month-old Beagles. Then the Beagles were fed and observed in Hubei Disease Control and Prevention Center. The canine infection model was evaluated and the results are shown as follows:1Clinical symptoms of rabies appeared around11days after inoculation, including refusal of food, reduced mobility, loss of fur, salivation, prostration, hydrophobia, paralysis and pharyngismus.2RT-PCR analysis revealed that RABV were detected in the saliva samples in three out of the nine dogs after showing clinical symptoms of rabies.3RT-PCR analysis showed that RABV was detected in the tongue, adrenal gland, heart, small intestine, lymph nodes of neck and cornea.4Biochemical analysis of serum and cerebrospinal fluid (CSF) showed that the number of peripheral blood leukocytes (WBC) or neutrophils (NEU) increased in infected dogs. The WBC counts and NEU counts were about17.73×109/L and13.03X109/L, respectively. The average of WBC and NEU counts were23.74×109/L and17.04×109/L, respectively. The total protein (TP) was significantly increased in cerebrospinal fluid, and the highest TP reached to5.1g/L.5Virus neutralizing antibody (VNA) titers in the serum and CSF did not significantly increase even at the time of euthanization and all of the VNA titers were below0.5IU/ml.6Inflammation, neuron swollen and local hemorrhage have been found in the infected brain. However, the Negri’s body and apoptosis were not observed.7Immunohistochemical analysis revealed that there were extensive RABV infection in the salivary glands and hippocampus, but very little in the cerebellum, brainstem or cerebral cortex.In conclusion, a canine model for rabies infection has been successfully established, which may be helpful for future study on the pathogenesis of RABV and the development of novel vaccines.