Guo Chunhe, Huang Yumao, Cong Peiqing, Liu Xiaohong, Chen Yaosheng, He Zuyong
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, North Third road, Guangzhou Higher Education Mega Center, Guangzhou, Guangdong, 510006, PR China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, 510642, PR China.
BMC Microbiol. 2014 Nov 18;14:273. doi: 10.1186/s12866-014-0273-8.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pig industry, causing high economic losses worldwide. Current vaccines have specific limitations in terms of their safety and efficacy, so the development of novel antiviral drugs is urgently required. The aim of this study was to evaluate the inhibitory effects and underlying molecular mechanisms of the antimicrobial peptide cecropin P1 (CP1) against PRRSV infection in vitro.
CP1 not only displayed extracellular virucidal activity against PRRSV, but also exerted a potent inhibitory effect when added either before, simultaneously with, or after viral inoculation. The inhibitory effect of CP1 occurred during viral attachment, but not at viral entry into Marc-145 cells. CP1 also inhibited viral particle release and attenuated virus-induced apoptosis during the late phase of infection. CP1 exerted similar inhibitory effects against PRRSV infection in porcine alveolar macrophages, the cells targeted by the virus in vivo during its infection of pigs. The expression of interleukin 6 was elevated by CP1 in porcine alveolar macrophages, which might contribute to its inhibition of PRRSV infection.
Collectively, our findings provide a new direction for the development of potential therapeutic drugs against PRRSV infection.
猪繁殖与呼吸综合征病毒(PRRSV)持续威胁着养猪业,在全球范围内造成了巨大的经济损失。目前的疫苗在安全性和有效性方面存在特定局限性,因此迫切需要开发新型抗病毒药物。本研究旨在评估抗菌肽天蚕素P1(CP1)对PRRSV体外感染的抑制作用及其潜在分子机制。
CP1不仅对PRRSV具有细胞外杀病毒活性,而且在病毒接种前、接种时或接种后添加均能发挥强大的抑制作用。CP1的抑制作用发生在病毒附着阶段,但在病毒进入Marc-145细胞时未起作用。CP1还抑制病毒颗粒释放,并在感染后期减轻病毒诱导的细胞凋亡。CP1对猪肺泡巨噬细胞中的PRRSV感染也有类似的抑制作用,猪肺泡巨噬细胞是病毒在感染猪时在体内的靶细胞。CP1可提高猪肺泡巨噬细胞中白细胞介素6的表达,这可能有助于其抑制PRRSV感染。
总体而言,我们的研究结果为开发抗PRRSV感染的潜在治疗药物提供了新方向。