Submitted to: Journal of Veterinary Diagnostic Investigation
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/31/2003
Publication Date: 9/1/2004
Citation: Liebler-Tenorio, E.M., Ridpath, J.F., Neill, J.D. 2004. Distribution of viral antigen and tissue lesions in persistent and acute infection with the homologous strain of noncytopathic bovine viral diarrhea virus. Journal of Veterinary Diagnostic Investigation. 16:388-396. Interpretive Summary: Bovine viral diarrhea virus (BVDV) is an economically important pathogen of cattle. Animals which are infected while they are fetuses may develop a persistent life long infection. These persistently infected animals never clear the virus from their system but do not become sick. However, if they come into contact with another animal they can spread the virus to that animal and that animal will develop clinical disease. The question asked in this study was why persistently infected animals do not develop clinical signs of illness. We isolated a BVDV strain from a persistently infected (PI) animal. We used this strain to infect other animals that had never been exposed to BVDV (acutely infected animals). We found that virus grew in the same tissues in both PI and acutely infected animals. The difference was that when the virus grew in cells in acutely infected animals the cells died. It was not the virus growing in these cells that killed them, because virus growing in cells of PI animals does not result in cell death. We think that cell death was caused by the animals own immune system. These results help us to understand the basis of the clinical disease seen with BVDV. Knowing the basis for the clinical disease may help us reduce the effects of BVDV infection in the future.
Technical Abstract: To assess the importance of host responses in the pathogenesis of lesions observed in acute bovine virus diarrhea virus (BVDV) infection of cattle, viral distribution and lesions were compared between calves born with persistent infection (PI) and after acute infection with the same BVDV isolate. Two PI calves from one dairy herd were necropsied. The PI viruses were characterized by sequencing and found to be identical. The isolated non cytopathogenic (ncp) BVDV2 strain RS886 was used to inoculate clinically healthy, seronegative calves which were 3 weeks to 3 months old. Nine calves received 10**6-10**7 TCID BVDV2-RS886 intranasally. Four additional animals served as non infected controls. Calves were necropsied at 3, 6, 9, and 13 days post inoculation (dpi). Viral antigen was detected by immunohistochemistry in frozen sections and lesions were evaluated in HE-stained paraplast sections. In the PI calves, a wide distribution of viral antigen was found in all tissues and was not associated with lesions. In the acutely infected calves, viral antigen was widespread in lymphoid tissues at 6 dpi, but had been mostly eliminated at 9 and 13 dpi. Depletion of lymphoid tissues was seen at 6, 9 and 13 dpi and repopulation at 9 and 13 dpi. In one of the calves at 13 dpi, severe arteritis was present in lymph nodes and myocardium. The fact that lesions were only observed in acute infection where the host immune system recognizes the virus indicates that host immune responses are important for the development of lesions caused by ncp BVDV.