Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28-4-1BB Signaling in Bovine PBMCs.
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.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Quan-Jiang
QJ
Song
College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, China.
Xiao-Gang
XG
Weng
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Dong-Jie
DJ
Cai
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Wang
W
Zhang
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Jiu-Feng
JF
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018106:CD28 Antigens / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006027:Glycosides / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000378:metabolism; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
D018106:CD28 Antigens; D016207:Cytokines; D006027:Glycosides; D007074:Immunoglobulin G; D047992:TNF Receptor-Associated Factor 2; C058049:forsythiaside