Verma Shailendra Kumar, Gupta Nimesh, Pattnaik Priyabrata, Babu J Pradeep, Rao P V Lakshmana, Kumar Subodh
Division of Microbiology, Defence Research and Development Establishment, Gwalior, India.
Protein Pept Lett. 2009;16(11):1334-41. doi: 10.2174/092986609789353709.
Japanese encephalitis virus (JEV) is a mosquito-borne viral zoonosis of public health importance. Global efforts have been made towards development of vaccine for prevention of Japanese encephalitis. The envelope protein of JEV is associated with viral binding to cellular receptors, membrane fusion, and the induction of protective neutralizing antibody response in hosts. Here we report that the antibodies raised against refolded domain III of envelope protein of JEV neutralize the JE virus and inhibit the JEV infection to Porcine Stable Kidney (PS) cells. A reverse transcriptase-PCR amplified gene encoding domain III of JEV envelope protein was cloned into pET28a+ vector and over expressed in E. coli. The recombinant JEV-DIII protein was purified by affinity chromatography under denaturing conditions. The rJEV-DIII was refolded by oxido-redux shuffle and purified to homogeneity by ion-exchange chromatography. Refolded rJEV-DIII was characterized using biochemical and biophysical methods. The polyclonal antibodies were raised against in vitro refolded rJEV-DIII protein in BALB/c mice with Freunds adjuvant. Ninety percent JEV is neutralized when the serum against refolded rJEV-DIII is used at a dilution of 1:80 as against 60.5% neutralization capacity with the same dilution of serum raised against denatured rJEV-DIII. The method of expression and purification of biologically functional rJEV-DIII protein described in this study may help in better understanding the biology of JE virus and the development of better vaccine candidate. Since the expression system uses E. coli as the heterologous host, the process is easy and amenable to inexpensive scale-up.
日本脑炎病毒(JEV)是一种具有公共卫生重要性的蚊媒病毒性人畜共患病。全球已致力于开发预防日本脑炎的疫苗。JEV的包膜蛋白与病毒与细胞受体的结合、膜融合以及宿主中保护性中和抗体反应的诱导有关。在此,我们报告针对JEV包膜蛋白重折叠的结构域III产生的抗体可中和JE病毒,并抑制JEV对猪稳定肾(PS)细胞的感染。通过逆转录酶 - PCR扩增编码JEV包膜蛋白结构域III的基因,并克隆到pET28a +载体中,在大肠杆菌中过量表达。重组JEV - DIII蛋白在变性条件下通过亲和层析纯化。rJEV - DIII通过氧化还原重排进行重折叠,并通过离子交换层析纯化至均一性。使用生化和生物物理方法对重折叠的rJEV - DIII进行表征。在BALB / c小鼠中用弗氏佐剂针对体外重折叠的rJEV - DIII蛋白产生多克隆抗体。当使用针对重折叠的rJEV - DIII的血清以1:80的稀释度时,90%的JEV被中和,而针对变性的rJEV - DIII的相同稀释度血清的中和能力为60.5%。本研究中描述的具有生物学功能的rJEV - DIII蛋白的表达和纯化方法可能有助于更好地理解JE病毒的生物学特性以及开发更好的候选疫苗。由于表达系统使用大肠杆菌作为异源宿主,该过程简单且适合低成本扩大规模。