Pacheco Juan M, Henry Tina M, O'Donnell Vivian K, Gregory Jason B, Mason Peter W
Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, U.S. Department of Agriculture, Greenport, New York 11944, USA.
J Virol. 2003 Dec;77(24):13017-27. doi: 10.1128/jvi.77.24.13017-13027.2003.
The genome of foot-and-mouth disease virus (FMDV) differs from that of other picornaviruses in that it encodes a larger 3A protein (>50% longer than poliovirus 3A), as well as three copies of protein 3B (also known as VPg). Previous studies have shown that a deletion of amino acids 93 to 102 of the 153-codon 3A protein is associated with an inability of a Taiwanese strain of FMDV (O/TAW/97) to cause disease in bovines. Recently, an Asian virus with a second 3A deletion (amino acids 133 to 143) has also been detected (N. J. Knowles et al., J. Virol. 75:1551-1556, 2001). Genetically engineered viruses harboring the amino acids 93 to 102 or 133 to 143 grew well in porcine cells but replicated poorly in bovine cells, whereas a genetically engineered derivative of the O/TAW/97 virus expressing a full-length 3A (strain A12) grew well in both cell types. Interestingly, a virus with a deletion spanning amino acid 93 to 144 also grew well in porcine cells and caused disease in swine. Further, genetically engineered viruses containing only a single copy of VPg were readily recovered with the full-length 3A, the deleted 3A (amino acids 93 to 102), or the "super" deleted forms of 3A (missing amino acids 93 to 144). All of the single-VPg viruses were attenuated in porcine cells and replicated poorly in bovine cells. The single-VPg viruses produced a mild disease in swine, indicating that the VPg copy number is an important determinant of host range and virulence. The association of VPg copy number with increased virulence in vivo may help to explain why all naturally occurring FMDVs have retained three copies of VPg.
口蹄疫病毒（FMDV）的基因组与其他小核糖核酸病毒的基因组不同，在于它编码一种更大的3A蛋白（比脊髓灰质炎病毒3A长50%以上），以及三个蛋白3B拷贝（也称为VPg）。先前的研究表明，153个密码子的3A蛋白中93至102位氨基酸的缺失与台湾口蹄疫病毒株（O/TAW/97）无法在牛中引起疾病有关。最近，还检测到一种具有第二次3A缺失（133至143位氨基酸）的亚洲病毒（N. J. Knowles等人，《病毒学杂志》75:1551 - 1556，2001年）。携带93至102位或133至143位氨基酸的基因工程病毒在猪细胞中生长良好，但在牛细胞中复制不佳，而表达全长3A的O/TAW/97病毒的基因工程衍生物（A12株）在两种细胞类型中均生长良好。有趣的是，一种缺失93至144位氨基酸的病毒在猪细胞中也生长良好，并在猪中引起疾病。此外，仅含有单个VPg拷贝的基因工程病毒很容易与全长3A、缺失的3A（93至102位氨基酸）或3A的“超级”缺失形式（缺失93至144位氨基酸）一起获得。所有单VPg病毒在猪细胞中都减毒，在牛细胞中复制不佳。单VPg病毒在猪中引起轻度疾病，表明VPg拷贝数是宿主范围和毒力的重要决定因素。VPg拷贝数与体内毒力增加之间的关联可能有助于解释为什么所有天然存在的口蹄疫病毒都保留了三个VPg拷贝。
