Interferon lambda (IFN-λ) plays an important role in inducing an antiviral state in mucosal surfaces and has been used as an effective biotherapeutic against several viral diseases. Here we performed a proof of concept study on the activity of a biologically active recombinant bovine IFN-λ (rIFN-λ) produced in eukaryotic cells against Bovine Viral Diarrhea Virus (BVDV) in cattle. We first confirmed the lack of toxicity of different concentrations of rIFN-λ in bovine peripheral blood cells and the safety of its subcutaneous application in calves in doses up to 12 IU/kg. The antiviral activity of the rIFN-λ against BVDV was assessed in calves that were inoculated with 6 IU/kg of rIFN-λ (n = 4) or mock-treated (n = 2) two days before and after challenge with a BVDV type-2 non-cytopathic strain. Mock-treated animals developed respiratory disease, shedded the virus from 4 to 7 days post-infection (dpi) and had viremia between 4 and 14 dpi. Conversely, calves treated with rIFN-λ did not develop clinical symptoms. The virus was not found in nasal secretions or sera. Only one animal had a positive viral RNA detection in serum at 7 dpi. All infected animals treated with rIFN-λ increased systemic type-I IFNs levels at 4 dpi. The antiviral treatment induced an earlier onset of the anti-BVDV neutralizing antibodies. Altogether, these results constitute the proof-of-principle of bovine IFN-λ as an antiviral biotherapeutic to protect cattle against the clinical disease caused by BVDV.

干扰素λ（IFN-λ）在诱导粘膜表面的抗病毒状态中起着重要作用，并已被用作针对多种病毒性疾病的有效生物疗法。在这里，我们对牛的牛病毒性腹泻病毒（BVDV）的真核细胞中产生的具有生物活性的重组牛IFN-λ（rIFN-λ）的活性进行了概念验证研究。我们首先证实了不同浓度的rIFN-λ在牛外周血细胞中没有毒性，并且以最高12 IU / kg的剂量在牛犊中皮下施用的安全性。在用BVDV型激发前后两天接种6 IU / kgrIFN-λ（n = 4）或模拟治疗（n = 2）的小牛中评估了rIFN-λ对BVDV的抗病毒活性。 -2非细胞病变菌株。模拟治疗的动物出现了呼吸系统疾病，在感染后（dpi）4到7天脱落病毒，病毒血症在4到14 dpi之间。相反，用rIFN-λ治疗的小牛没有出现临床症状。在鼻分泌物或血清中未发现该病毒。只有一只动物在7 dpi时血清中的病毒RNA检测阳性。用rIFN-λ治疗的所有感染动物在4 dpi时增加了全身I型IFN水平。抗病毒治疗诱导抗BVDV中和抗体的早期发作。总而言之，这些结果构成了牛IFN-λ作为抗病毒生物治疗剂的原理证明，可以保护牛免受BVDV引起的临床疾病的侵害。只有一只动物在7 dpi时血清中的病毒RNA检测阳性。用rIFN-λ治疗的所有感染动物在4 dpi时增加了全身I型IFN水平。抗病毒治疗诱导抗BVDV中和抗体的早期发作。总之，这些结果构成了牛IFN-λ作为抗病毒生物治疗剂的原理证明，可以保护牛免受BVDV引起的临床疾病的侵害。只有一只动物在7 dpi时血清中的病毒RNA检测阳性。用rIFN-λ治疗的所有感染动物在4 dpi时增加了全身I型IFN水平。抗病毒治疗诱导抗BVDV中和抗体的早期发作。总之，这些结果构成了牛IFN-λ作为抗病毒生物治疗剂的原理证明，可以保护牛免受BVDV引起的临床疾病的侵害。