Abstract

Bovine viral diarrhea virus (BVDV) causes a severe threat to the cattle industry due to ineffective control measures. Gypenoside is the primary component of Gynostemma pentaphyllum, which has potential medicinal value and has been widely applied as a food additive and herbal supplement. However, little is known about the antiviral effects of gypenoside. The present study aimed to explore the antiviral activities of gypenoside against BVDV infection. The inhibitory activity of gypenoside against BVDV was assessed by using virus titration and performing Western blotting, quantitative reverse transcription PCR (RT-qPCR), and immunofluorescence assays in MDBK cells. We found that gypenoside exhibited high anti-BVDV activity by interfering with the viral attachment to and internalization in cells. The study showed that BVDV infection inhibits apoptosis of infected cells from escaping the innate defense of host cells. Our data further demonstrated that gypenoside inhibited BVDV infection by electively activating the apoptosis of BVDV-infected cells for execution, as evidenced by the regulation of the expression of the apoptosis-related protein, promotion of caspase-3 activation, and display of positive TUNEL staining; no toxicity was observed in non-infected cells. Collectively, the data identified that gypenoside exerts an anti-BVDV-infection role by inhibiting viral attachment and internalization and selectively purging virally infected cells. Therefore, our study will contribute to the development of a novel prophylactic and therapeutic strategy against BVDV infection.

Highlights

  • Bovine viral diarrhea virus (BVDV) is a pathogen that is distributed worldwide and is responsible for significant economic losses in the cattle industry [1]

  • In order to confirm the antiviral effect of gypenoside treatment, Madin–Darby Bovine Kidney (MDBK) cells were treated with escalating concentrations of gypenoside for 1 h before being infected with the BVDV BJ175170 and BJ1305 isolate strains at up to 24 hpi

  • The results showed that, compared Meanto the uninfec while, gypenoside treatment upregulated BCL2-associated X protein (Bax) and cleaved caspase-3 protein expression control, BVDV infection upregulated the expression of claudin 1 and the occludin pro and downregulated the expression of B-cell lymphoma-2 (Bcl-2) protein in BVDV-infected cells compared to the (Figure 4A)

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Summary

Introduction

Bovine viral diarrhea virus (BVDV) is a pathogen that is distributed worldwide and is responsible for significant economic losses in the cattle industry [1]. BVDV belongs to the genus Pestivirus of the Flaviviridae family, which includes both the border disease virus in sheep and the causative agent of classical swine fever [3,4]. RNA molecule of about 12.3 kb in length [5] It contains a unique open reading frame encoding a large polyprotein processed into 10–11 structural and non-structural proteins: Npro -C-Erns -E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B [6]. According to the genetic and antigenic differences, BVDV can be divided into three different species: BVDV-1, BVDV-2, and BVDV-3 [7]. Two biotypes of BVDV are further sub-divided into two phenotypic biotypes—cytopathic (CP) and

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