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

Seong, Giyong; Lee, Jin-Sol; Lee, Kyung Hyun; Shin, Seung-Uk; Yoon, Ji Young; Choi, Kyoung-Seong

doi:10.1007/s00705-015-2665-y

Cited by 8 publications

(9 citation statements)

References 24 publications

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“…The difference in virulence between the two strains was evidenced by an earlier onset of viremia in the mice infected with the NY-93 strain than in those bearing the 98-124 strain, and by the induction of a peak of systemic TNF-α in all the animals infected with 98-124. None of the infected mice developed clinical disease, coincident with previous reports (26,41); with the infection being verified by only the presence of viremia, both by virus titration and RT-PCR.…”

Section: Discussionsupporting

confidence: 88%

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

et al. 2020

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Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre-and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.

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Section: Discussionsupporting

confidence: 88%

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

et al. 2020

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“…In the distribution of viral antigens, the previous study (20) showed that viral antigens were detected in the spleen of all infected mice from days 4 through 14 of post-infection and suggested that the spleen is the most reliable tissue for BVDV antigen detection in a murine model. In the present study, we found that viral antigens were consistently detected in both the spleen and blood.…”

Section: Discussionmentioning

confidence: 93%

“…Fifteen mice were assigned into the CP BVDV-, NCP BVDV-, and mock-infection groups with 5 mice per group. Challenge was performed by intraperitoneal (IP) injection of 0.4 mL of culture medium containing 10 6 copies/mL of each virus ( 20 ). Mock-infected mice were given 0.4 mL of DMEM (Gibco, Grand Island, NY, USA) via IP injection.…”

Section: Methodsmentioning

confidence: 99%

PD-1 Blockade Restores the Proliferation of Peripheral Blood Lymphocyte and Inhibits Lymphocyte Apoptosis in a BALB/c Mouse Model of CP BVDV Acute Infection

Liu

Chen

et al. 2021

Front. Immunol.

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Acute infection of bovine viral diarrhea virus (BVDV) is associated with immune dysfunction and can cause peripheral blood lymphopenia and lymphocyte apoptosis. Our previous study has confirmed that programmed death-1 (PD-1) blockade inhibits peripheral blood lymphocytes (PBL) apoptosis and restores proliferation and anti-viral immune functions of lymphocytes after BVDV infection in vitro. However, the situation in vivo remains to be further studied and confirmed. Therefore, in this study, we established a BALB/c mouse model of acute BVDV infection with cytopathic (CP) BVDV (strain NADL) and non-cytopathic (NCP) BVDV (strain NY-1). Then, we examined the mRNA and protein levels of PD-1 and programmed death-ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMC) from BVDV-infected mice and analyzed the effects of PD-1 blockade on the proportions of CD3+, CD4+, and CD8+ T cell subsets, the apoptosis and proliferation of PBL, and the production of IL-2 and IFN-γ. We found that leukopenia, lymphocytopenia, and thrombocytopenia were developed in both CP and NCP BVDV-infected mice at day 7 of post-infection. The mRNA and protein expression of PD-1 and PD-L1 were significantly upregulated in CP and NCP BVDV-infected mice. Moreover, PD-1/PD-L1 upregulation was accompanied by leukopenia and lymphopenia. Additionally, PD-1 blockade inhibited PBL apoptosis and virus replication, restored the proportions of CD3+, CD4+, and CD8+ T cell subsets, and increased IFN-γ production and p-ERK expression in BVDV-infected mice. However, blocking PD-1 did not significantly affect PBL proliferation and IL-2 production in NCP BVDV-infected mice. Our findings further confirmed the immunomodulatory role of PD-1 in peripheral blood lymphocytopenia in vivo and provided a scientific basis for exploring the molecular mechanism of immune dysfunction caused by acute BVDV infection.

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“…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.…”

Section: Resultados Desarrollo Del Modelo Murino De Infección Por El unclassified

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

Quintana

Barone

Forlenza

et al. 2018

Journal of Virological Methods

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Low-cost high-throughput methods applicable to any virus strain are required for screening antiviral compounds against multiple field strains. Colorimetric cell-viability assays are used for this purpose as long as the viruses are cytopathic (CP) in cell culture. However, bovine viral diarrhoea virus (BVDV) strains circulating in the field are mostly non-cytopathic (NCP). An In Cell-ELISA aimed to measure viral infectivity by detecting a conserved protein produced during viral replication (non-structural protein 3, "NS3") was developed. The ELISA is performed without harvesting the cells, directly on the 96-wells culture plate. NS3 In Cell-ELISA was tested for its ability to assess BVDV-specific antiviral activity of recombinant bovine type I and III IFNs. Results correlated to those measured by qRT-PCR and virus titration. NS3 In Cell-ELISA was also efficient in estimating the IC50 of two compounds with different antiviral activity. Estimation of the 50% inhibition dose of each IFN using six BVDV strains of different biotype and genotype showed that CP strains were more susceptible to both IFNs than NCP, while type 2 NCP viruses were more sensitive to IFN-I. The In Cell-ELISA format using a detector antibody against a conserved non-structural protein can be potentially applied to accurately measure infectivity of any viral strain.

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

Cited by 8 publications

References 24 publications

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

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

PD-1 Blockade Restores the Proliferation of Peripheral Blood Lymphocyte and Inhibits Lymphocyte Apoptosis in a BALB/c Mouse Model of CP BVDV Acute Infection

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

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