Abstract
Non-cytopathic (ncp) type 2 bovine viral diarrhea virus (BVDV-2) is widely prevalent in Argentina causing high mortality rates in cattle herds. In this study, we characterized an Argentinean ncp BVDV-2 field isolate (98-124) compared to a high-virulence reference strain (NY-93), using in silico analysis, in vitro assays, and in vivo infections of colostrum-deprived calves (CDC) to compare pathogenic characters and virulence. In vitro infection of bovine peripheral blood mononuclear cells (PBMC) with BVDV 98-124 induced necrosis shortly after infection while NY-93 strain increased the apoptotic rate in infected cells. Experimental infection of CDC (n = 4 each) with these strains caused an enteric syndrome. High pyrexia was detected in both groups. Viremia and shedding were more prolonged in the CDC infected with the NY-93 strain. In addition, NY-93 infection elicited a severe lymphopenia that lasted for 14 days, whereas 98-124 strain reduced the leukocyte counts for 5 days. All infected animals had a diminished lymphoproliferation activity in response to a mitogen. Neutralizing and anti-NS3 antibodies were detected 3 weeks after infection in all infected calves. Virulence was associated with a more severe clinical score, prolonged immune-suppression, and a greater window for transmission. Studies of apoptosis/necrosis performed after in vitro PBMC infection also revealed differences between both strains that might be correlated to the in vivo pathogenesis. Our results identified 98-124 as a low-virulence strain.
Highlights
Bovine viral diarrhea virus (BVDV) is a common pathogen of ruminants worldwide
Peripheral blood mononuclear cells (PBMC) from BVDVnegative calves were infected in vitro with both type-2 strains and the viability of the infected cells was assessed by measuring apoptosis and necrosis using Annexin V/7-AAD staining
The BVDV-2b 98-124 Argentinean isolate had in silico, in vitro, and in vivo features to classify it as a typical low-virulence type 2 strain
Summary
Infections with BVDV lead to significant economic losses and have an important impact on the cattle industry [1,2,3,4,5,6]. By infecting cells of the immune system, BVDV evokes an immunosuppression leading to a decreased immune response to other infectious agents [7]. The immunosuppression elicited by BVDV includes a transient leukopenia in calves [8, 9], with diminished counts in peripheral B and T lymphocytes [10, 11], as well as monocytopenia and neutropenia [11, 12] with functional impairment of monocytes, dendritic cells, neutrophils, and lymphocytes [9, 11, 13, 14].
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