The Pathogenicity Of Bovine Viral Diarrhoea Virus 1p Subgenotype

Bovine viral diarrhoea virus(BVDV)is one of the main pathogens of the bovine respiratory disease complex(BRDC),which infect various economic animals such as calve.BVDV infection not only causes respiratory symptoms but also immunosuppression in infected animals.In addition,the co-infections oc-curring between BVDV and other pathogens of BRDC can aggravate the BRDC in infected animals,causing heavy economic losses.BVDV can be divided into two genotypes,BVDV-1 and BVDV-2,and there are at least twenty-two subgenotypes in BVDV-1 and three in BVDV-2.The pathogenicity and cross-immune response among different subgenotypes are different.BVDV-1p is a major subgenotype prevalent in China.This study intends to carry out the related work to fill the gap of pathogenicity research on BVDV-1p.In addition,given the variety of known and unknown BRDC pathogens in calves that might impact the accuracy of animal pathogenicity tests,this study carries out the test using laboratory animals with clear biological backgrounds aiming at the pathogenicity of BVDV-1p.This study also using labor-atory animal to evaluate the pathogenicity of the high-generation BVDV-1p strain and its protection against heterologous BVDV strain as an attenuated vaccine candidate.First,after infection with noncytopathic(NCP)BVDV-1p strain 3877,the infected calve occurred viremia,shed the virus through the respiratory and digestive tracts,showed the clinical symptoms of‘biphasic fever',nasal fluid increase,diarrhoea,and leukopenia.Secondly,mice,guinea pigs and rabbits were used as experimental animals,respectively,to study the pathogenicity of the BVDV-1p strain 3877 in this study.In mice,after strain 3877 infection,the weight growth rate and the number of WBCs in blood were decreased,mild hyperplasia occurred in lung alveolar epithelial cells,and the virus was detected in lungs,liver,spleen,kidneys and gonads.In rabbits,the specific thermal reactions occurred at 2 to 4 day post-infection,and the depletion of lymphocytes in the spleen was observed post-BVDV-1p infection.In addition,the virus was detected in many organs of rab-bits such as lungs,spleen,liver,and kidneys.Although leukopenia and mild proliferation of lung alveolar epithelial cells were observed,and the virus was detected in the lung and spleen in guinea pigs.The strain3877 grew poorly in guinea pigs.Furthermore,treatment with dexamethasone or serial passage in vivo did not increase the viral titre of strain 3877 in the organs of guinea pigs.Thirdly,this study evaluated the pathogenicity of the high-generation strain BVDV-1p 3877 P288strain in the rabbit model.The stain was serially passaged 227 times on MDBK cell in vitro.After infec-tion with the 3877 P228 strain,the temperature of specific thermal reactions in rabbits and the viral titre in the organs of rabbits were lower than that of the parent strain infected rabbits.In addition,no patho-logical changes in the organs were observed in 3877 P228 strain infected rabbits.Through whole gene sequencing,it was found that the sense mutations of the viral genome occurred in E^rns gene,E1 gene,E2gene,P7 gene,NS2 gene,NS4B gene,NS5A gene and NS5B gene after serial passage in vitro.Finally,this study evaluated the effectiveness of the 3877 P228 strain as an attenuated vaccine can-didate in rabbit model.The titers of neutralizing antibodies against BVDV are different between the pa-rental strain and the heterologous strain after the booster immunization in rabbit sera.However,whether challenged with the parental strain or the heterologous ones,the periods of the viremia and the virus shedding from the nasal cavity in the immunized groups were shorter than those in the none immunized groups,and the viral load in blood and nose swab from the immunized groups were also lower.In summary,NCP BVDV-1p 3877 strain is pathogenic to calves.And mice and rabbits can be used as the infection models for BVDV-1p 3877 strain.BVDV-1p high-generation strain 3877 P228 is attenu-ated in rabbit model.As an attenuated vaccine candidate strain,strain 3877 P228 can protect immunized rabbits against challenges with parental and heterologous strains of BVDV-1.