Pathogenesis of leukopenia in calves experimentally infected with non-cytopathic type II bovine viral diarrhea virus

This study is an investigation of the pathogenesis of the hematological abnormalities observed in calves experimentally infected with non-cytopathic (ncp) type II bovine viral diarrhea virus (BVDV). Calves were intransally inoculated with a virulent strain, 24515, or a low virulence strain, 11Q. Calves inoculated with the virulent strain developed anorexia, diarrhea and respiratory signs. Calves inoculated with the low virulence strain exhibited no overt clinical signs. Fevers were significantly higher in 24515-inoculated calves. Serial peripheral blood and bone marrow samples were obtained before and after virus inoculation and monitored for changes in the circulating and bone marrow cell populations, respectively. Bone marrow samples were evaluated for the presence of viral antigen in hematopoietic cells with immunocytochemistry using the monoclonal antibody 15CS. Calves inoculated with both viruses developed leukopenia, neutropenia, lymphopenia and thrombocytopenia to varying degrees. White blood cell counts were significantly lower and persisted longer with the virulent 24515 strain. The bone marrow myeloid maturation pool decreased concurrently with development of leukopenia in animals inoculated with either virus but depletion persisted longer in 24515-inoculated animals. The bone marrow proliferation pool increased in proportion to the decrease in the maturation pool in 11Q-inoculated calves, but took 4 days longer to increase in 24515-inoculated animals. Viral antigen in bone marrow cells was sparse and transient in 24515-inoculated animals but was present when peripheral blood counts were lowest. Viral antigen was never demonstrated in 11Q-inoculated calves. Megakaryocytes were the predominant cell type exhibiting positive staining. These experiments demonstrated that infection with ncp type II BVDV strains of varying virulence result in leukopenia. The virulent isolate caused a delay in the production of myeloid cells which could potentially compromise the ability of the host to satisfy tissue demands for neutrophils and contribute to secondary bacterial infections. Infection of myeloid precursor cells appeared to contribute to this delay. Ability to delay production of bone marrow myeloid cells and infection of megakaryocytes may enhance virulence, contributing to the ability of certain ncp type II BVDV strains to induce severe disease.