Experimental infection with cytopathic bovine viral diarrhea virus in mice induces megakaryopoiesis in the spleen and bone marrow

Abstract

Here, we infected mice with cytopathic bovine viral diarrhea virus 1 (cp BVDV1) by oral inoculation and investigated the effects of infection by histopathological, immunohistochemical (IHC), hematological methods. Twelve mice were infected, and samples were obtained at day 2, 5, and 9 postinfection (pi). Most of the infected mice exhibited clinical signs of illness such as reduced movement, crouching, loose feces, loss of appetite, and reduced water intake. Blood samples from six mice were positive for BVDV based on reverse transcription polymerase chain reaction (RT-PCR). Blood analysis also revealed thrombocytopenia and lymphopenia. Viral antigens were detected in the spleen (12/12), bone marrow (12/12), and/or mesenteric lymph nodes (4/12) of all infected mice by IHC analysis. The spleens showed significant histopathological changes including (i) substantially increased numbers of megakaryocytes, (ii) lymphocyte depletion, and (iii) hemorrhages. The bone marrow also had an increased number of megakaryocytes, although this increase was not as strong as it was in the spleen. Severe lymphoid depletion was observed in the mesenteric lymph nodes. Viral infections were present in the lymphocytes but not detected in megakaryocytes of the spleen, bone marrow, or mesenteric lymph nodes. These results suggest that the increased numbers of megakaryocytes may be a direct result of BVDV infection. BVDV infection in mice following oral inoculation of cp BVDV1 leads to megakaryopoiesis in the spleen and bone marrow to replenish the platelets.

A direct high-throughput in Cell-ELISA for measuring infectivity of cytopathic and non-cytopathic bovine viral diarrhoea virus strains applied to the assessment of antiviral activity

“…En un primer experimento, dos grupos de 8 ratones BALB/c (hembras, 6-8 semanas de vida) fueron inoculados por vía intra-peritoneal (IP) con 0,4 ml de una dosis de 5.10 5 DICT50/ml de dos cepas del VDVB. Esta dosis fue la establecida por Seong y colaboradores en su trabajo de puesta a punto de este modelo [144]- [146]. Cuatro animales se dejaron como control sin infectar, y solamente recibieron 0,4 ml de medio de infección.…”

“…La evaluación de la actividad antiviral de los IFNr in vitro arrojó resultados favorables para continuar con el estudio en modelos animales in vivo. Previo a realizar estudios en bovinos decidimos realizar una primera prueba de concepto en el modelo murino para evaluar la actividad de los IFN-α y λ. Trabajos publicados por Seong y col [144], [145] reportan la utilización de ratones BALB/c como modelo de infección para VDVB. De esta manera establecimos primero si los animales se infectaban con cepas de nuestro interés y caracterizamos el perfil de esa infección.…”

Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bovine viral diarrhoea (BVD)

“…With the exception of rabbits mentioned under Parameter 3 a range of non‐arteriodactyls, including horses, cats, dogs, guinea pigs, mice and embryonated chicken eggs have previously been reported not to be susceptible to infection with BVDV (Baker et al., ), although recent work has suggested that mice can be infected when inoculated by oral and intra‐nasal challenge (Seong et al., , ).…”

“…to be susceptible to infection with BVDV (Baker et al, 1954), although recent work has suggested that mice can be infected when inoculated by oral and intra-nasal challenge (Seong et al, 2015(Seong et al, , 2016.…”

In-vivo Activity of IFN-λ and IFN-α Against Bovine-Viral-Diarrhea Virus in a Mouse Model

“…We also developed a method to easily measure infectivity of BVDV by visualizing infected cells using a monoclonal antibody against a non-structural protein (NS3), considered a marker of virus replication (25). Recently, a mouse model of BVDV infection was set-up and tested with several strains showing that mice developed viremia without clinically manifest disease (26,27). In this study, we made use of all these tools, set up the BALB/c infection model for 2-well characterized type-2 ncp BVDV strains (28) and evaluated the efficacy of prophylaxis and treatment with IFN-α and IFN-λ in reducing BVDV infection.…”