Abstract

Bovine viral diarrhea virus (BVDV), the causative agent of bovine viral diarrhea/mucosal disease (BVD/MD), is an important pathogen of cattle and other wild animals throughout the world. BVDV infection typically leads to an impaired immune response in cattle. In the present study, we investigated the effect of Forsythoside A (FTA) on BVDV infection of bovine peripheral blood mononuclear cells (PBMCs). We found that Forsythoside A could not only promote proliferation of PBMCs and T cells activation but also inhibit the replication of BVDV as well as apoptosis induced by BVDV. FTA treatment could counteract the BVDV-induced overproduction of IFN-γ to maintain the immune homeostasis in bovine PBMCs. At same time, FTA can enhance the secretion of IL-2. What’s more, BVDV promotes the expression of CD28, 4-1BB and TRAF-2, which can be modulated by FTA. Our data suggest that FTA protects PBMCs from BVDV infection possibly via TRAF2-dependent CD28–4-1BB signaling, which may activate PBMCs in response to BVDV infection. Therefore, this aids in the development of an effective adjuvant for vaccines against BVDV and other specific FTA-based therapies for preventing BVDV infection.

Highlights

  • Bovine viral diarrhea virus (BVDV) is a member of the Pestivirus genus of the Flaviviridae family, with a worldwide distribution, and the cause of severe economic loss

  • There were more living cells in peripheral blood mononuclear cells (PBMCs) treated with BVDV plus Forsythoside A (FTA) than in cells only infected with BVDV at 48 and 72 h after stimulation (P = 0.001 and P = 0.006, respectively)

  • At 24 h post incubation with BVDV, there was no difference observed in the number of BVDV RNA copies between PBMCs stimulated with FTA plus BVDV and BVDV alone

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Summary

Introduction

Bovine viral diarrhea virus (BVDV) is a member of the Pestivirus genus of the Flaviviridae family, with a worldwide distribution, and the cause of severe economic loss. BVDV infection can cause several cattle diseases, in the form of both transient or persistent infections, thought to be the reservior of viral transimission [1,2]. BVDV is a single-stranded positive-sense RNA virus, 12.3–12.5 kb in length, and contains one large open reading frame (ORF) flanked by 5’ and 3’ untranslated regions (UTRs). BVDV is divided into two distinct species: BVDV-1 and BVDV-2. Both species are categorized as cytopathogenic (cp) and noncytopathogenic (ncp) based on their effect in cultured cells [1,4]. The Oregon C24V strain of BVDV is utilized in this study and causes fever, leukopenia, virema, a decreased number of lymphocytes in calves, and cytopathic effects [5,6]

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