【PNAS】揭示感冒病毒引发感染的分子机制
PNAS：揭示感冒病毒引发感染的分子机制
2014/01/06 21:13:07
一般情况下我们一年会患2-3次感冒，但是普通感冒病毒感染机体的分子机制并不是完全清楚。近日，来自维也纳大学等处的研究者就清楚地解析了普通感冒病毒感染机体的分子机制，相关研究刊登于国际杂志_PNAS_上。
感冒病毒（鼻病毒）是一种较小的球形颗粒病毒，病毒包裹的遗传物质缠绕在蛋白质外壳（病毒衣壳）上，研究者在文章中揭示了病毒RNA释放衣壳以及有效感染人类机体的分子机制。
研究者Dieter Blaas说道，我们在文章中揭示了感冒病毒感染宿主细胞的分子结构，以及病毒RNA释放和复制的细节。研究者发现病毒RNA的构象以及其与病毒内在的衣壳间的相互作用不断发生着变化。
鼻病毒也会引发脊髓灰质炎和甲型肝炎的发生，该病毒属于微小核醣核酸病毒科，这项研究也为揭示其它疾病，比如甲肝等疾病的发病机理提供了一定思路。然而关于鼻病毒感染的很多机制目前仍不清楚，研究者表示，后期还需要进行大量研究工作来揭示病毒引发疾病的细节，这对于未来开发抵御病毒的药物或者新型疗法非常重要，本文也为后期的研究提供了一定的研究基础。
Uncoating of common cold virus is preceded by RNA switching as determined by X-ray and cryo-EM analyses of the subviral A-particle
Angela Pickl-Herka, Daniel Luqueb, Laia Vives-Adriánd, Jordi Querol-Audíd, Damià Garrigae, Benes L. Trusf, Nuria Verdaguerd, Dieter Blaasa, and José R. Castónb
During infection, viruses undergo conformational changes that lead to delivery of their genome into host cytosol. In human rhinovirus A2, this conversion is triggered by exposure to acid pH in the endosome. The first subviral intermediate, the A-particle, is expanded and has lost the internal viral protein 4 (VP4), but retains its RNA genome. The nucleic acid is subsequently released, presumably through one of the large pores that open at the icosahedral twofold axes, and is transferred along a conduit in the endosomal membrane; the remaining empty capsids, termed B-particles, are shuttled to lysosomes for degradation. Previous structural analyses revealed important differences between the native protein shell and the empty capsid. Nonetheless, little is known of A-particle architecture or conformation of the RNA core. Using 3D cryo-electron microscopy and X-ray crystallography, we found notable changes in RNA–protein contacts during conversion of native virus into the A-particle uncoating intermediate. In the native virion, we confirmed interaction of nucleotide(s) with Trp38 of VP2 and identified additional contacts with the VP1 N terminus. Study of A-particle structure showed that the VP2 contact is maintained, that VP1 interactions are lost after exit of the VP1 N-terminal extension, and that the RNA also interacts with residues of the VP3 N terminus at the fivefold axis. These associations lead to formation of a well-ordered RNA layer beneath the protein shell, suggesting that these interactions guide ordered RNA egress.
Source from 生物谷