Li Pinghua, Bai Xingwen, Sun Pu, Lu Zengjun, Cao Weijun, Wu Run, Yin Hong, Liu Zaixin
Veterinary College of Gansu Agricultural University, Lanzhou 730070, China.
Wei Sheng Wu Xue Bao. 2011 Mar;51(3):423-8.
Foot-and-Mouth Disease Virus (FMDV) initiates infection by binding to integrin receptors via a highly conserved Arg-Gly-Asp (RGD) sequence found in the G-H loop of the structural protein VP1. However, FMDV is an RNA virus, which harbors the evolutionary potential to render the RGD motif dispensable upon changes in constant environment. We studied mutation of RGD motif upon short-time passages FMDV Asial/JS/China/2005 field strain in different host.
VP1 gene was amplified from Asial/JS/China/05 field strain, the fourth passage virus in sulking mice (MF4) of the above strain and the virus isolated from a pig housing with cattle inoculated with the above strain followed eight passages in BHK-21 cell (PBF8) by RT-PCR, and the VP1 genes were sequenced and their deduced amino acid sequences were compared with each other.
Dominant population with RGD and Arg-Ser-Asp (RSD) receptor recognition site motif was generated after four passages of Asial/JS/China/2005 field virus in sulking mice and another dominant population with Arg-Asp-Asp (RDD) motif was produced after eight passages the virus isolated from housing pig with cattle inoculated with the above field strain.
This study indicated that the dominant FMDV virus populations with RSD or RDD receptor binding site instead of original RGD motif were produced upon short-time evolution of FMDV field isolates with RGD motif in different environment. These studies not only increase number of viable mutants with substitutions in the RGD region, but also these profoundly altered, but viable, mutants with different receptor recognition site will provide useful tools for studies of cell recognition by FMDV and host tropism modifications.
口蹄疫病毒（FMDV）通过结构蛋白VP1的G-H环中高度保守的精氨酸-甘氨酸-天冬氨酸（RGD）序列与整合素受体结合来启动感染。然而，FMDV是一种RNA病毒，具有在不断变化的环境中使RGD基序变得可有可无的进化潜力。我们研究了FMDV亚洲1型/JS/中国/2005流行毒株在不同宿主中短期传代后RGD基序的突变情况。
通过RT-PCR从亚洲1型/JS/中国/05流行毒株、该毒株在乳鼠中的第四代传代病毒（MF4）以及从接种了上述毒株的猪舍中分离出并在BHK-21细胞中传代8次的病毒（PBF8）中扩增VP1基因，对VP1基因进行测序，并将其推导的氨基酸序列相互比较。
亚洲1型/JS/中国/2005流行毒株在乳鼠中传代4次后产生了具有RGD和精氨酸-丝氨酸-天冬氨酸（RSD）受体识别位点基序的优势群体，而从接种了上述流行毒株的猪舍中分离出的病毒传代8次后产生了具有精氨酸-天冬氨酸-天冬氨酸（RDD）基序的另一个优势群体。
本研究表明，具有RGD基序的FMDV流行毒株在不同环境中短期进化后产生了具有RSD或RDD受体结合位点而非原始RGD基序的优势FMDV病毒群体。这些研究不仅增加了RGD区域发生替代的存活突变体的数量，而且这些具有不同受体识别位点的深刻改变但仍存活的突变体将为研究FMDV的细胞识别和宿主嗜性修饰提供有用的工具。
