一种负载猪干扰素α/γ的pH触发自释放腐植酸水凝胶通过口服达到了抗伪狂犬病病毒的效果。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Maoyuan Sun, Yongli Shi, Baishi Lei, Wuchao Zhang, Jingjing Feng, Shenghu Ge, Wanzhe Yuan, Kuan Zhao
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引用次数: 0

摘要

干扰素 α(IFNα)和干扰素 γ(IFNγ)在介导抗病毒活性和免疫调节等关键生物功能方面发挥着举足轻重的作用。然而,单体 IFN 的疗效有限,而且只能依靠注射给药。为解决这一问题,我们成功表达并纯化了重组猪 IFNα 和 IFNγ 融合蛋白(rPoIFNα/γ)。此外,我们还开发了一种 pH 触发的腐植酸水凝胶给药系统,它能有效保护 rPoIFNα/γ 免受胃酸降解,从而提高其口服生物利用度。在体外实验中,腐植酸水凝胶和 rPoIFNα/γ 均未对猪肾-15(PK-15)细胞产生细胞毒性作用。rPoIFNα/γ 能有效抑制水泡性口炎病毒和伪狂犬病毒(PRV)的复制,其抗病毒活性约为 104 U/mL。扫描电子显微镜显示,腐植酸水凝胶具有疏松多孔的蜂窝状结构。傅立叶变换红外光谱分析证实,IFNα/γ@PAMgel 水凝胶能有效吸附 rPoIFNα/γ,显示出良好的 IFN 负载能力。体外实验显示,IFNα/γ@PAMgel 在 pH 值为 7.4 时会迅速膨胀并释放 IFNα/γ,而在 pH 值为 1.2 时则不会。小鼠口服 IFNα/γ@PAMgel 可促进 CD4+ 和 CD8+ 细胞的增殖和分化。此外,感染 PRV 并接受 IFNα/γ@PAMgel 治疗的小鼠血清中干扰素刺激基因的转录水平升高,死亡率降低,各种组织中的病毒载量减少,器官损伤程度减轻。总之,本研究表明口服 IFNα/γ@PAMgel 具有抗病毒和免疫调节作用,突出了其作为 PRV 感染治疗剂的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A pH-triggered self-releasing humic acid hydrogel loaded with porcine interferon α/γ achieves anti-pseudorabies virus effects by oral administration.

Interferon α (IFNα) and interferon γ (IFNγ) play pivotal roles in mediating crucial biological functions, including antiviral activity and immune regulation. However, the efficacy of monomeric IFN is limited, and its administration relies solely on injection. To address this issue, we successfully expressed and purified a recombinant porcine IFNα and IFNγ fusion protein (rPoIFNα/γ). Furthermore, we developed a pH-triggered humic acid hydrogel delivery system that effectively protects rPoIFNα/γ from gastric acid degradation, enhancing its oral bioavailability. Neither the humic acid hydrogel nor rPoIFNα/γ exhibited cytotoxic effects on porcine kidney-15 (PK-15) cells in vitro. The replication of vesicular stomatitis virus and pseudorabies virus (PRV) was effectively inhibited by rPoIFNα/γ, resulting in an antiviral activity of approximately 104 U/mL. Scanning electron microscopy revealed that the humic acid hydrogel had a loose and porous honeycomb structure. The IFNα/γ@PAMgel hydrogel effectively adsorbed rPoIFNα/γ, as confirmed by Fourier transform infrared spectroscopy analysis, demonstrating a favourable IFN-loading capacity. In vitro experiments revealed that IFNα/γ@PAMgel swelled and released IFNα/γ rapidly at pH 7.4 but not at pH 1.2. The oral administration of IFNα/γ@PAMgel in mice enhanced the proliferation and differentiation of CD4+ and CD8+ cells. Additionally, mice infected with PRV and treated with IFNα/γ@PAMgel presented increased transcription levels of interferon-stimulated genes in the serum, reduced mortality rates, lower viral loads in various tissues, and decreased levels of organ damage. In conclusion, this study demonstrates that orally administered IFNα/γ@PAMgel has antiviral and immunomodulatory effects, highlighting its potential as a therapeutic agent against PRV infection.

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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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