Structural proteins of West Nile virus are a major determinant of infectious particle production and fitness in astrocytes.
Structural proteins of West Nile virus are a major determinant of infectious particle production and fitness in astrocytes.
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DOI：
10.1099/vir.0.065474-0
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发表时间：
2014-09
期刊：
影响因子：
--
通讯作者：
Fredericksen BL
中科院分区：
文献类型：
--
作者：
Hussmann KL;Vandergaast R;Zheng K;Hoover LI;Fredericksen BL
与神经致病株WNV-NY相比，星形胶质细胞对非神经致病性西尼罗病毒(WNV)株WNV-MAD78的抵抗力增强的分子基础尚不清楚。在这里，我们证明了星形胶质细胞对WNV-MAD78敏感性的降低是由于细胞活动和病毒决定因素的共同作用。对病毒颗粒的分析表明，星形胶质细胞来源的WNV-MAD78颗粒比WNV-NY颗粒的感染性更低。此外，抑制细胞内的呋喃类蛋白水解酶增加了WNV-MAD78感染颗粒在星形胶质细胞中的产生，这表明这些细胞中高水平的呋喃类蛋白水解酶活性以细胞和菌株特异性的方式抑制WNV-MAD78的复制。此外，对重组病毒的分析表明，与WNV-NY相比，WNV-MAD78的结构蛋白导致了颗粒传染性的降低和感染性颗粒的产生。因此，西尼罗河病毒病毒粒子的组成也是星形胶质细胞内病毒适合性的主要决定因素，并可能有助于西尼罗河病毒在中枢神经系统内的传播。WNV-MAD78结构基因是否通过与细胞呋喃类蛋白水解酶活性相同的机制来减少病毒复制和颗粒感染性，或者这两个决定因素是否通过不同的途径发挥作用仍有待确定。
The molecular basis for the increased resistance of astrocytes to a non-neuropathogenic strain of West Nile virus (WNV), WNV-MAD78, compared with the neuropathogenic strain WNV-NY remains unclear. Here, we demonstrated that the reduced susceptibility of astrocytes to WNV-MAD78 is due to a combination of both cellular activities as well as viral determinants. Analyses of the viral particle indicated that astrocyte-derived WNV-MAD78 particles were less infectious than those of WNV-NY. Additionally, inhibition of cellular furin-like proteases increased WNV-MAD78 infectious particle production in astrocytes, suggesting that high levels of furin-like protease activity within these cells acted in a cell- and strain-specific manner to inhibit WNV-MAD78 replication. Moreover, analysis of recombinant viruses indicated that the structural proteins of WNV-MAD78 were responsible for decreased particle infectivity and the corresponding reduction in infectious particle production compared with WNV-NY. Thus, the composition of the WNV virion was also a major determinant for viral fitness within astrocytes and may contribute to WNV propagation within the central nervous system. Whether the WNV-MAD78 structural genes reduce virus replication and particle infectivity through the same mechanism as the cellular furin-like protease activity or whether these two determinants function through distinct pathways remains to be determined.
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