Jiang Yibo, Khan Faheem Ahmed, Pandupuspitasari Nuruliarizki Shinta, Kadariya Ishwari, Cheng Zhangrui, Ren Yuwei, Chen Xing, Zhou Ao, Yang Liguo, Kong Dexin, Zhang Shujun
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Int J Mol Sci. 2013 Dec 9;14(12):23955-79. doi: 10.3390/ijms141223955.
Porcine reproductive and respiratory syndrome virus (PRRSV) can infect pigs and cause enormous economic losses to the pig industry worldwide. Porcine sialoadhesin (pSN) and CD163 have been identified as key viral receptors on porcine alveolar macrophages (PAM), a main target cell infected by PRRSV. In this study, the protein structures of amino acids 1-119 from the pSN and cSN (cattle sialoadhesin) N-termini (excluding the 19-amino acid signal peptide) were modeled via homology modeling based on mSN (mouse sialoadhesin) template structures using bioinformatics tools. Subsequently, pSN and cSN homology structures were superposed onto the mSN protein structure to predict the binding sites of pSN. As a validation experiment, the SN N-terminus (including the wild-type and site-directed-mutant-types of pSN and cSN) was cloned and expressed as a SN-GFP chimera protein. The binding activity between SN and PRRSV was confirmed by WB (Western blotting), FAR-WB (far Western blotting), ELISA (enzyme-linked immunosorbent assay) and immunofluorescence assay. We found that the S107 amino acid residue in the pSN N-terminal played a crucial role in forming a special cavity, as well as a hydrogen bond for enhancing PRRSV binding during PRRSV infection. S107 may be glycosylated during PRRSV infection and may also be involved in forming the cavity for binding PRRSV along with other sites, including W2, Y44, S45, R97, R105, W106 and V109. Additionally, S107 might also be important for pSN binding with PRRSV. However, the function of these binding sites must be confirmed by further studies.
猪繁殖与呼吸综合征病毒(PRRSV)可感染猪,并给全球养猪业造成巨大经济损失。猪唾液酸粘附素(pSN)和CD163已被确定为猪肺泡巨噬细胞(PAM)上的关键病毒受体,PAM是PRRSV感染的主要靶细胞。在本研究中,使用生物信息学工具,基于mSN(小鼠唾液酸粘附素)模板结构,通过同源建模对pSN和cSN(牛唾液酸粘附素)N端1 - 119个氨基酸(不包括19个氨基酸的信号肽)的蛋白质结构进行建模。随后,将pSN和cSN同源结构叠加到mSN蛋白质结构上,以预测pSN的结合位点。作为验证实验,克隆了SN N端(包括pSN和cSN的野生型和定点突变型)并表达为SN - GFP嵌合蛋白。通过蛋白质免疫印迹法(WB)、远蛋白质免疫印迹法(FAR - WB)、酶联免疫吸附测定(ELISA)和免疫荧光测定法证实了SN与PRRSV之间的结合活性。我们发现,pSN N端的S107氨基酸残基在形成特殊腔以及在PRRSV感染期间增强PRRSV结合的氢键方面起着关键作用。S107在PRRSV感染期间可能被糖基化,并且可能还与其他位点(包括W2、Y44、S45、R97、R105、W106和V109)一起参与形成结合PRRSV的腔。此外,S107对于pSN与PRRSV的结合可能也很重要。然而,这些结合位点的功能必须通过进一步研究来证实。