Institute for Molecular Virology, University of Wisconsin, 1525 Linden Drive, Madison, WI 53706, United States of America.
Virology. 2014 Jan 5;448:82-90. doi: 10.1016/j.virol.2013.10.004. Epub 2013 Oct 20.
Human rhinoviruses of the RV-C species are recently discovered pathogens with greater clinical significance than isolates in the RV-A+B species. The RV-C cannot be propagated in typical culture systems; so much of the virology is necessarily derivative, relying on comparative genomics, relative to the better studied RV-A+B. We developed a bioinformatics-based structural model for a C15 isolate. The model showed the VP1-3 capsid proteins retain their fundamental cores relative to the RV-A+B, but conserved, internal RV-C residues affect the shape and charge of the VP1 hydrophobic pocket that confers antiviral drug susceptibility. When predictions of the model were tested in organ cultures or ALI systems with recombinant C15 virus, there was a resistance to capsid-binding drugs, including pleconaril, BTA-188, WIN56291, WIN52035 and WIN52084. Unique to all RV-C, the model predicts conserved amino acids within the pocket and capsid surface pore leading to the pocket may correlate with this activity.
人鼻病毒的 RV-C 种属是最近发现的病原体，其临床意义比 RV-A+B 种属的分离株更大。RV-C 不能在典型的培养系统中繁殖；因此，相对于研究得更好的 RV-A+B，病毒学的很大一部分必然是衍生的，依赖于比较基因组学。我们为 C15 分离株开发了一种基于生物信息学的结构模型。该模型显示 VP1-3 衣壳蛋白相对于 RV-A+B 保留了其基本核心，但保守的内部 RV-C 残基会影响赋予抗病毒药物敏感性的 VP1 疏水性口袋的形状和电荷。当模型的预测在含有重组 C15 病毒的器官培养物或 ALI 系统中进行测试时，发现对衣壳结合药物（包括普乐可复、BTA-188、WIN56291、WIN52035 和 WIN52084）具有耐药性。该模型预测的 RV-C 所有种属特有的是，位于口袋内和衣壳表面孔通向口袋的保守氨基酸可能与这种活性相关。
