Tissue Distribution And Pathogenicity Assay Of The Pseudorabies Virus Variant Strain JS-2012 And Its Gene-deleted Derivative (JS-2012-ΔgI/gE) Infected In Mice

Pseudorabies (PR) is an acute infectious disease caused by pseudorabies virus (PRV). It often causes reproductive failure or stillbirth in sow pigs, neurologic symptoms, dyspnea,and high mortality in piglets. It causes a great economic loss in pig industry. Vaccination is the effective way to prevente and treat the PR disease. However, since 2011, infection has broken out in large-scale pig farms in China. Through isolation and identification of the pathogen it finally revealed that the disease was caused by a variant of pseudorabies virus. The re-emerged pseudorabies virus JS-2012 isolated from Jiangsu province and its gene-deleted derivative PRV JS-2012-A gl/gE strain constructed in our laboratory were used in this study with 105TCED50 by intranasal and intramuscular injection challenge with 6 weeks old SPF KM mice. Then the infected mice were killed in regular time, took samples from heart, liver, spleen, lung, kidney, brain, cerebellum, and medulla, spinal cord, nerve, for the quantitative PCR and histopathological experimental study. We used mice as a model to understand re-emerged pseudorabies virus JS-2012 infection in animals, which can provide references for the research of its pathogenic mechanism and provide theoretical support for clinical prevention and treatment of pseudorabies disease.Clinical symptoms showed that:The mice challenged with variant strain JS-2012 appeared typical symptoms of pseudorabies virus:including odd itching, dyspnea, ataxia and other neurological symptoms, however, the onset time of the mice infected by the gene-deleted strain was later than variant strain JS-2012, the clinical symptoms were not obvious, and several mice survived.At pathologic autopsy:the liver swelled and hemorrhage, however, the spleen shrinked. In the lung cells swelle and hemorrhage phenomenon happened from the center to edge. Control groups were normal. This experiment also found that parts of the dying mice in the abdomen swelling, gastrointestinal cheerily.The histopathological results showed that:the structure of lung tissue was not clear and hemorrhaged, a large number of lymphocytes infiltrated in interstitial. It suggested that the never system and respiratory system in SPF mice were severely injured.Quantitative PCR analysis showed that:in intranasal infected mice, the virus replicated in the mouth nasal mucosa at first, after 24 hours virus distributed in body organs, and then the virus was mainly propagated in the nervous system and cardiovascular organs, especially in the trigeminal nerve and lung tissues with the largest viral load, and there was a transient viremia. After 36 hours intramuscular mice infected in spleen, the immune organs, while the content of the virus in the spinal cord, nerves, and blood was very high as well. Therefore we speculate intramuscular infected in mice mainly from the injection site through the spinal cord and blood to other body organs and tissue, eventually the virus colonizated in the central nervous, acute infection led to death in mice. The re-emerged pseudorabies virus strain JS-2012 were earlier and stronger than its gene-deleted derivative JS-2012-AgI/gE in the time of onset and pathogenicity, both mainly infected nervous syetem.