Katpally Umesh, Smith Thomas J
Donald Danforth Plant Science Center, 975 North Warson Road, St. Louis, Missouri 63132, USA.
J Virol. 2007 Jun;81(12):6307-15. doi: 10.1128/JVI.00441-07. Epub 2007 Apr 11.
Human rhinovirus 14 (HRV14) is a member of the rhinovirus genus, which belongs to the picornavirus family, which includes clinically and economically important members, such as poliovirus, foot-and-mouth disease virus, and endomyocarditis virus. Capsid stability plays an important role in the viral infection process, in that it needs to be stable enough to move from cell to cell and yet be able to release its genetic material upon the appropriate environmental cues from the host cell. It has been suggested that certain host cell molecules, "pocket factors," bind to the WIN drug-binding cavity beneath the canyon floor and provide transient stability to a number of the picornaviruses. To directly test this hypothesis, HRV14 was mutated in (V1188M, C1199W, and V1188M/C1199W) and around (S1223G) the drug-binding pocket. Infectivity, limited proteolysis, and matrix-assisted laser desorption ionization analyses indicate that filling the drug-binding pocket with bulky side chains is not deleterious to the viral life cycle and lends some stabilization to the capsid. In contrast, studies with the S1223G mutant suggest that this mutation at least partially overcomes WIN drug-mediated inhibition of cell attachment and capsid breathing. Finally, HRV16, which is inherently more stable than HRV14 in a number of respects, was found to "breathe" only at 37 degrees C and did not tolerate stabilizing mutations in the drug-binding cavity. These results suggest that it is the drug-binding cavity itself and not the putative pocket factor that is crucial for the capsid dynamics, which is, in turn, necessary for infection.
人鼻病毒14型（HRV14）是鼻病毒属的成员，鼻病毒属属于小核糖核酸病毒科，该科包含临床上和经济上重要的成员，如脊髓灰质炎病毒、口蹄疫病毒和心内膜炎病毒。衣壳稳定性在病毒感染过程中起着重要作用，因为它需要足够稳定以便在细胞间移动，同时又能够在宿主细胞的适当环境信号作用下释放其遗传物质。有人提出某些宿主细胞分子，即“口袋因子”，会结合到峡谷底部下方的WIN药物结合腔，并为多种小核糖核酸病毒提供瞬时稳定性。为了直接验证这一假设，对HRV14在药物结合口袋内部（V1188M、C1199W和V1188M/C1199W）以及周围（S1223G）进行了突变。感染性、有限蛋白酶解和基质辅助激光解吸电离分析表明，用庞大侧链填充药物结合口袋对病毒生命周期无害，并且能为衣壳提供一定程度的稳定性。相比之下，对S1223G突变体的研究表明，这种突变至少部分克服了WIN药物介导的对细胞附着和衣壳呼吸的抑制作用。最后，发现HRV16在许多方面本质上比HRV14更稳定，它仅在37摄氏度时“呼吸”，并且不能耐受药物结合腔内的稳定化突变。这些结果表明，对于衣壳动力学至关重要的是药物结合腔本身而非假定的口袋因子，而衣壳动力学对于感染又是必需的。
