Sun Min, Yu Zeyanqiu, Ma Jiale, Pan Zihao, Lu Chengping, Yao Huochun
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Vet Microbiol. 2017 Jun;205:6-13. doi: 10.1016/j.vetmic.2017.04.031. Epub 2017 May 1.
Porcine epidemic diarrhea virus (PEDV), is the etiological agent of porcine epidemic diarrhea virus (PED), causes high mortality with severe vomiting, diarrhea, and dehydration in swine farms. In this study, the PEDV strain 85-7 could be proliferated effectively in MARC-145 cells, and caused a distinct inhibition of the expression of interferon-β (IFN-β, encoded by IFNB1), which suggested that a full understanding how this virus manipulates the host immune responses is critical in the fight against the spread of PEDV. We found that, the infection of PEDV strain 85-7 significantly downregulated HSP27 production in MARC-145 cells, and overexpression of HSP27 (encoded by HSPB1) decreased the virus titer by about 28-fold. Further study revealed that HSP27 could significantly activate the NF-κB phosphorylation, and thus increase the mRNA level of IFNB1 and downstream interferon-stimulated genes (ISGs) in MARC-145 cells. Indeed, treatment with IFN-β and the ISGs, including murine myxovirus resistance 1 and 2 (Mx1 and Mx2), showed direct anti-PEDV activity. Notably, the antiviral activity and transcription of the antiviral effectors induced by overexpression of HSP27 could be counteracted by the knockdown of IFNB1 via RNA interference, indicating that HSP27 was an upstream regulator of the intracellular antiviral effect against PEDV infection. This study is the first to link HSP27 to PEDV replication via the innate immunity response, which contributed to further clarify the mechanism of PEDV infection and the development of novel antiviral therapies.
猪流行性腹泻病毒（PEDV）是猪流行性腹泻（PED）的病原体，可导致猪场猪只高死亡率，并伴有严重呕吐、腹泻和脱水症状。在本研究中，PEDV毒株85-7能在MARC-145细胞中有效增殖，并显著抑制干扰素-β（IFN-β，由IFNB1编码）的表达，这表明全面了解该病毒如何操纵宿主免疫反应对于对抗PEDV传播至关重要。我们发现，PEDV毒株85-7感染显著下调了MARC-145细胞中HSP27的产生，而过表达HSP27（由HSPB1编码）可使病毒滴度降低约28倍。进一步研究表明，HSP27可显著激活NF-κB磷酸化，从而增加MARC-145细胞中IFNB1和下游干扰素刺激基因（ISG）的mRNA水平。事实上，用IFN-β和ISG（包括小鼠抗黏液病毒1和2，即Mx1和Mx2）进行处理显示出直接的抗PEDV活性。值得注意的是，通过RNA干扰敲低IFNB1可抵消HSP27过表达诱导的抗病毒活性和抗病毒效应分子的转录，这表明HSP27是针对PEDV感染的细胞内抗病毒效应的上游调节因子。本研究首次通过先天免疫反应将HSP27与PEDV复制联系起来，这有助于进一步阐明PEDV感染机制和开发新型抗病毒疗法。
