VP1 sequencing of all human rhinovirus serotypes: Insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds
VP1 sequencing of all human rhinovirus serotypes: Insights into genus phylogeny and susceptibility to antiviral capsid-binding compounds
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DOI：
10.1128/jvi.78.7.3663-3674.2004
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Pevear, DC
中科院分区：
文献类型：
--
作者：
Ledford, RM;Patel, NR;Pevear, DC
鼻病毒是人类最常见的传染性病原体。它们是不发热的病毒性上呼吸道感染（普通感冒）的主要病因。人鼻病毒（hrv）包括小鼻病毒科中的一个属。这个属有大约100个血清典型的不同成员。为了更好地了解它们的系统发育关系，对所有已知HRV血清型和一个未分型分离株（HRV- hanks）的病毒衣壳主要表面蛋白VPl的核苷酸序列进行了测定。对推导出的氨基酸序列数据的系统发育分析支持先前的研究，将该属细分为两个种，包含除了一种HRV血清型（HRV-87）之外的所有HRV血清型。75种HRV血清型和HRV- hanks属于HRV- a种，25种HRV血清型属于HRV- b种。VPl内部有一个疏水性口袋，小分子抗病毒化合物如pleconaril可以结合并抑制与病毒衣壳相关的功能。对构成该口袋的氨基酸的分析表明，该序列与病毒对pleconaril抑制的易感性密切相关。此外，从参加pleconaril临床试验的患者身上恢复的易感变异病毒中观察到的氨基酸变化与那些赋予药物自然表型抗性的病毒不同。这些观察结果表明，根据药物结合袋的序列分析，有可能区分对衣壳功能抑制剂具有天然抗性的鼻病毒和由于抗病毒药物选择压力而从易感病毒群体中出现的鼻病毒。
Rhinoviruses are the most common infectious agents of humans. They are the principal etiologic agents of afebrile viral upper-respiratory-tract infections (the common cold). Human rhinoviruses (HRVs) comprise a genus within the family Picornaviridae. There are > 100 serotypically distinct members of this genus. In order to better understand their phylogenetic relationship, the nucleotide sequence for the major surface protein of the virus capsid, VPl, was determined for all known HRV serotypes and one untyped isolate (HRV-Hanks). Phylogenetic analysis of deduced amino acid sequence data support previous studies subdividing the genus into two species containing all but one HRV serotype (HRV-87). Seventy-five HRV serotypes and HRV-Hanks belong to species HRV-A, and twenty-five HRV serotypes belong to species HRV-B. Located within VPl is a hydrophobic pocket into which small-molecule antiviral compounds such as pleconaril bind and inhibit functions associated with the virus capsid. Analyses of the amino acids that constitute this pocket indicate that the sequence correlates strongly with virus susceptibility to pleconaril inhibition. Further, amino acid changes observed in reduced susceptibility variant viruses recovered from patients enrolled in clinical trials with pleconaril were distinct from those that confer natural phenotypic resistance to the drug. These observations suggest that it is possible to differentiate rhinoviruses naturally resistant to capsid function inhibitors from those that emerge from susceptible virus populations as a result of antiviral drug selection pressure based on sequence analysis of the drug-binding pocket.