Agricultural Research Service, US Department of Agriculture, Plum Island Animal Disease Center, Greenport, New York 11944-0848, USA.
Virology. 2012 Jan 5;422(1):37-45. doi: 10.1016/j.virol.2011.09.031. Epub 2011 Oct 27.
FMDV O1 subtype undergoes antigenic variation under diverse growth conditions. Of particular interest is the amino acid variation observed at position 56 within the structural protein VP3. Selective pressures influence whether histidine (H) or arginine (R) is present at this position, ultimately influencing in vitro plaque morphology and in vivo pathogenesis in cattle. Using reverse genetics techniques, we have constructed FMDV type O1 Campos variants differing only at VP3 position 56, possessing either an H or R (O1Ca-VP3-56H and O1Ca-VP3-56R, respectively), and characterized their in vitro phenotype and virulence in the natural host. Both viruses showed similar growth kinetics in vitro. Conversely, they had distinct temperature-sensitivity (ts) and displayed significantly different pathogenic profiles in cattle and swine. O1Ca-VP3-56H was thermo stable and induced typical clinical signs of FMD, whereas O1Ca-VP3-56R presented a ts phenotype and was nonpathogenic unless VP3 position 56 reverted in vivo to either H or cysteine (C).
口蹄疫病毒 O1 亚型在不同的生长条件下会发生抗原变异。特别值得关注的是结构蛋白 VP3 中第 56 位氨基酸的变异。选择压力会影响组氨酸 (H) 或精氨酸 (R) 是否存在于该位置，最终影响体外斑块形态和牛体内的发病机制。我们使用反向遗传学技术构建了仅在 VP3 位置 56 处存在差异的口蹄疫病毒 O1 坎波斯变体，分别具有 H 或 R（分别为 O1Ca-VP3-56H 和 O1Ca-VP3-56R），并对其在体外表型和天然宿主中的毒力进行了表征。两种病毒在体外的生长动力学相似。相反，它们的温度敏感性（ts）不同，在牛和猪中的致病性谱也有显著差异。O1Ca-VP3-56H 具有热稳定性，会引发典型的口蹄疫临床症状，而 O1Ca-VP3-56R 则表现出 ts 表型，除非 VP3 位置 56 在体内恢复为 H 或半胱氨酸 (C)，否则它是无毒的。
