据悉，河南农业大学张改平院士研究团队于2016年11月23日在国际病毒学权威期刊《Journal of Virology》同时在线发表了两篇论文，题目分别为“Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain (SRCR5) from Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection”和“MicroRNA-373 Facilitated the Replication of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) by Its Negative Regulation of Type I Interferon Induction”。
其中，第一篇文章报道了该团队通过蛋白质晶体学技术在国际上率先解析了PRRSV入侵必需受体CD163关键结构域SRCR5的三维结构，发现了CD163介导PRRSV入侵的关键氨基酸位点；第二篇文章报道了该团队利用RNA高通量测序技术首次发现PRRSV感染后通过nsp9和N蛋白上调Sp1的表达促进miR-373的转录，而后者通过靶向I-型干扰素信号转导通路中的关键分子抑制I-型干扰素的产生从而促进了病毒复制。
猪繁殖与呼吸综合征（PRRS）是一种以母猪流产和各生长阶段猪呼吸障碍为主要特征的重要的病毒性传染病。自从上世纪90年代该病在美国和加拿大发现以来，在全球范围内广泛传播，是全球猪病控制上的一大难题。1995年以来，该病一直在我国长期流行，给国内生猪养殖业带来难以估量的经济损失。这两项研究成果对PRRS新型药物开发、新型疫苗研制具有重要意义，研究获得了国家自然科学基金重大项目 “猪繁殖与呼吸综合症病毒致病机理研究”（编号31490600）资助。
Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain (SRCR5) from Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection
Abstract:
Porcine reproductive and respiratory syndrome (PRRS) has become an economically critical factor in swine industry since its world-wide spread in the 1990s. The infection of its causative agent, PRRS virus (PRRSV), is proven to be mediated by an indispensable receptor, porcine CD163 (pCD163) and the fifth scavenger receptor cysteine-rich domain (SRCR5) is essential for the virus infection. However, the structural details and specific residues of pCD163 SRCR5 involved in infection have not been defined yet. In this study, we prepared recombinant pCD163 SRCR5 in Drosophila Schneider 2 (S2) cells and determined its crystal structure at a high resolution of 2.0 Å. This structure includes a markedly long loop region and shows a special electrostatic potential, which are significantly different from other members in scavenger receptor cysteine-rich superfamily (SRCR-SF). Subsequently we carried out structure-based mutational studies to identify the arginine residue at position 561 (Arg561) in the long loop region is important for PRRSV infection. Further we showed Arg561 probably takes effect on the binding of pCD163 to PRRSV during the virus invasion. Altogether the current work provides the first view of CD163 SRCR domain, expands our knowledge of the invasion mechanism of PRRSV, and supports a molecular basis for prevention and control of the virus.
原文链接：https://www.ncbi.nlm.nih.gov/pubmed/27881657
MicroRNA-373 Facilitated the Replication of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) by Its Negative Regulation of Type I Interferon Induction
Abstract
microRNAs (miRNAs) played an important role in the regulation of immune response. Previous studies have indicated that dysregulating the miRNAs may lead to the immunosuppression of porcine reproductive and respiratory syndrome virus (PRRSV). However, it's not clear about how PRRSV regulated the expression of host miRNA which may make the immune escape or promote the replication of the virus. The present work suggested that PRRSV up-regulated the expression of miR-373 through elevating the expression of specificity protein 1 (Sp1) in MARC-145 cells. Furthermore, this work demonstrated that miR-373 promoted the replication of PRRSV since miR-373 was a novel negative miRNA to the production of interferon (IFN)-βby targeting nuclear factor I (NFI) A, NFIB, interleukin-1 receptor-associated kinase (IRAK)1, IRAK4 and interferon regulatory factor (IRF) 1. This paper also found that both NFIA and NFIB were the novel proteins for inducing the production of IFN-βand both of them could inhibit the replication of PRRSV. In conclusion, PRRSV up-regulated the expression of miR-373 by elevating the expression of Sp1 and hijacked the host miR-373 to promote the replication of PRRSV by negatively regulating the production of IFN-β.
原文链接：https://www.ncbi.nlm.nih.gov/pubmed/?term=MicroRNA-373+Facilitated+the+Replication+of+Porcine+Reproductive+and+Respiratory+Syndrome+Virus+(PRRSV)+by+Its+Negative+Regulation+of+Type+I+Interferon+Induction
本期编辑：胚芽鞘