Laboratory of Molecular Genetics, Institute for Frontier Life and Medical Sciences, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Laboratory of Molecular and Cellular Immunology, Graduate School of Biostudies, Kyoto University, Shogoin Kawahara-cho, Sakyo-ku, Kyoto, Japan.
Int Immunol. 2019 Nov 8;31(12):811-821. doi: 10.1093/intimm/dxz054.
Double-stranded RNA (dsRNA) is well characterized as an inducer of anti-viral interferon responses. We previously reported that dsRNA extracted from a specific edible plant possesses an immune-modulating capacity to confer, in mice, resistance against respiratory viruses, including the H1N1 strain of the influenza A virus (IAV). We report here that the systemic immune-activating capacity of the plant-derived dsRNA protected mice from infection by a highly virulent H5N1 strain of the IAV. In addition, subcutaneous inoculation of the dsRNA together with the inactivated virion of the H5N1 strain of the IAV suppressed the lethality of the viral infection as compared with individual inoculation of either dsRNA or HA protein, suggesting its potential usage as a vaccination adjuvant. Moreover, intra-peritoneal inoculation of the dsRNA limited the growth of B16-F10 melanoma cells through the activation of NK cells in murine models. Taken together, this study demonstrated the systemic immune-modulating capacity of a plant-derived dsRNA and its potential for nucleic acid-based clinical applications.
双链 RNA(dsRNA)是一种众所周知的抗病毒干扰素反应诱导剂。我们之前曾报道,从一种特定的食用植物中提取的 dsRNA 具有免疫调节能力,可使小鼠对包括甲型流感病毒(IAV)H1N1 株在内的呼吸道病毒产生抗性。我们在此报告称,植物源性 dsRNA 的全身免疫激活能力可保护小鼠免受高致病性 H5N1 型 IAV 的感染。此外,与单独接种 dsRNA 或 HA 蛋白相比,皮下接种 dsRNA 与 H5N1 型 IAV 的灭活病毒颗粒一起可抑制病毒感染的致死性,表明其可能用作疫苗佐剂。此外,dsRNA 的腹腔内接种通过激活 NK 细胞在小鼠模型中限制了 B16-F10 黑色素瘤细胞的生长。综上所述,本研究证明了植物源性 dsRNA 的全身免疫调节能力及其在核酸临床应用方面的潜力。