Instituto de Virología e Innovaciones Tecnológicas. IVIT, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) - Instituto Nacional de Tecnología Agropecuaria (INTA). Nicolás Repetto y Los Reseros s/n. Hurlingham, Buenos Aires, Argentina.
Área de Investigación en Sanidad Animal IIACS-CIAP- Estación Experimental Agropecuaria EEA, INTA Cerrillos, Salta, Argentina.
Vet Immunol Immunopathol. 2020 Dec;230:110145. doi: 10.1016/j.vetimm.2020.110145. Epub 2020 Nov 4.
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）在诱导黏膜表面的抗病毒状态方面发挥着重要作用，已被用作针对多种病毒病的有效生物治疗药物。在此，我们针对在真核细胞中产生的具有生物活性的重组牛干扰素 λ（rIFN-λ）对牛病毒性腹泻病毒（BVDV）在牛中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 在牛外周血单个核细胞中无毒性，并且在高达 12 IU/kg 的剂量下其在小牛中的皮下应用是安全的。rIFN-λ 对 BVDV 的抗病毒活性在接种 rIFN-λ（n=4）或模拟处理（n=2）的小牛中进行了评估，接种剂量为 6 IU/kg，在攻毒前 2 天和攻毒后 2 天。模拟处理的动物发生呼吸道疾病，在感染后 4 至 7 天（dpi）排毒，并在 4 至 14 dpi 期间出现病毒血症。相比之下，用 rIFN-λ 处理的小牛未出现临床症状。鼻腔分泌物或血清中均未检测到病毒。只有 1 只动物在 7 dpi 时血清中出现病毒 RNA 检测阳性。所有用 rIFN-λ 处理的感染动物在 4 dpi 时均增加了全身性 I 型干扰素水平。抗病毒治疗可更早地诱导抗 BVDV 中和抗体的产生。综上所述，这些结果证明了牛干扰素 λ 作为一种抗病毒生物疗法，可用于保护牛免受 BVDV 引起的临床疾病。
