Thibaut Hendrik Jan, van der Schaar Hilde M, Lanke Kjerstin H W, Verbeken Erik, Andrews Martin, Leyssen Pieter, Neyts Johan, van Kuppeveld Frank J M
Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
J Virol. 2014 Mar;88(5):3048-51. doi: 10.1128/JVI.03177-13. Epub 2013 Dec 26.
Coxsackieviruses require phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) for replication but can bypass this need by an H57Y mutation in protein 3A (3A-H57Y). We show that mutant coxsackievirus is not outcompeted by wild-type virus during 10 passages in vitro. In mice, the mutant virus proved as virulent as wild-type virus, even when mice were treated with a PI4KIIIβ inhibitor. Our data suggest that upon emergence, the 3A-H57Y mutant has the fitness to establish a resistant population with a virulence similar to that of wild-type virus.
柯萨奇病毒的复制需要磷脂酰肌醇-4-激酶IIIβ（PI4KIIIβ），但可通过蛋白3A中的H57Y突变（3A-H57Y）绕过这一需求。我们发现，在体外传代10次的过程中，突变型柯萨奇病毒不会被野生型病毒淘汰。在小鼠中，即使给小鼠使用PI4KIIIβ抑制剂，突变病毒也与野生型病毒一样具有毒性。我们的数据表明，3A-H57Y突变体一旦出现，就具备形成一个与野生型病毒毒力相似的抗性群体的适应性。
