猪口蹄疫病毒受体通用亚基αv的基因克隆及序列分析

Cloning and Sequence Analysis of cDNA Encoding Porcine αv Subunit for FMDV Receptor

摘要:

病毒受体是病毒宿主范围和组织嗜性的决定因素。研究发现，至少有四种整联蛋白αvβ1、αvβ3、αvβ6、αvβ8是口蹄疫病毒(FMDV)的受体，其中αv是4种受体的通用亚基。首次从口蹄疫病毒实验感染猪的肺组织中克隆到了通用亚基αv基因并对其核苷酸序列和推导的氨基酸序列进行了比较分析。猪αv亚基基因的编码区含有3141个核苷酸，编码1046个氨基酸，其N-端30个氨基酸为信号肽，其后的胞外域、跨膜区、胞浆域分别由955、29、32个氨基酸组成；胞外域含有11个潜在的糖基化位点(NXT/NXS)、2个Ca²⁺结合位点(DX［D/N］XDGXXD)、18个半胱氨酸残基。猪αv基因与牛、人、猕猴、家鼠、鸡、犬的αv基因的核苷酸序列同源性分别为93.3%、91.5%、91.4%、85.6%、73.2%、89.9%，推导的氨基酸序列同源性分别为96.3%、94.6%、94.1%、90.8%、81.6%、93.8%，猪与牛αv亚基同源性最高，表明受体αv亚基可能与口蹄疫病毒的宿主范围有关。

Abstract:

Receptors play a crucial role in determining the pathogenesis and tissue tropism of virus. Foot-and-mouth disease virus（FMDV）has been showed to use four integrins, αvβ1, αvβ3, αvβ6 and αvβ8 as receptors to initiate infection. In this study, the porcine integrin αv gene was cloned by RT-PCR from the lung tissue of healed pig infected experimently with FMDV, and compared its nucleotide and deduced amino acid sequence with the αv gene of other animals. The 3141bp cDNA of bovine integrin αv encodes a polypeptide of 1046 amino acids consisting of a 30-residue putative signal peptide, a 955-residue ectodomain, a 29-residue transmembrane domain, and a 32-residue cytoplasmic domain. The ectodomain contains 11 potential N-linked glycosylation sites（NXT/NXS）, 2 calcium binding domains(DX［D/N］XDGXXD) and 18 cysteine residues. The nucleotide sequence similarities of integrin αv between pig and cattle, human, rheses monkey, house mouse, chicken, dog are 93.3%, 91.5%, 91.4%, 85.6%, 73.2% and 89.9% respectively; and the amino acid sequence similarities are 96.3%, 94.6%,94.1%, 90.8%, 81.6% and 93.8%, respectively. The αv gene of cattle and pig exhibited the highest sequence homology. It is possible that host tropism of FMDV may related to divergence in receptors among different species.