Noncytopathic bovine viral diarrhea virus 2 impairs virus control in a mouse model

Abstract Objective Bovine viral diarrhea virus (BVDV) is an economically important viral pathogen. BVDV is classified into two distinct species: BVDV1 and BVDV2. Both these species consist of two biotypes: cytopathic (cp) and non-cytopathic (ncp), differing in their ability to induce cytopathogenic effects in cultured cells. In this study, we investigated the immunological differences between ncp BVDV1 and ncp BVDV2 infections. Materials and methods Specific pathogen-free BALB/c mice (6–8 wk old) were used. The challenge was performed by IP injection of 5 ′ 105 TCID50 of ncp BVDV1 or ncp BVDV2. Each BVDV strains- and mock-inoculated mice were sacrificed on days 4, 7, 10, and 14 post-inoculation (pi). Each tissues and blood were harvested. BVDV antigen detection, immunohistochemical staining was performed on mouse tissues. Spleens were used for flow cytometry. Cytokines and chemokines were detected separately by using a mouse CBA inflammation kit. Results Viral antigens were detected in the spleens of all infected mice from days 4 through 14 and also found in the mesenteric lymph nodes, GALT, heart, kidney, intestine, and BALT of some infected mice. In ncp BVDV2-infected mice, flow cytometric analysis revealed markedly fewer CD4+ and CD8+ T lymphocytes and lower expression of CD80/CD86 and I-A/I-E than those in ncp BVDV1-infected mice. IL-6 and MCP-1 was higher in the plasma of ncp BVDV2- than that in the plasma of ncp BVDV1-infected mice. Discussion Our results demonstrate that ncp BVDV1 and ncp BVDV2 interact differently with the host innate immune response in vivo. These findings highlight an important distinction between ncp BVDV1 and ncp BVDV2, and suggest that ncp BVDV2 impairs host’s virus control and enhances virus dissemination.