Host-Dependent Modifications of Packaged Alphavirus Genomic RNA Influence Virus Replication in Mammalian Cells.
Host-Dependent Modifications of Packaged Alphavirus Genomic RNA Influence Virus Replication in Mammalian Cells.
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DOI：
10.3390/v14122606
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发表时间：
2022-11-23
期刊：
影响因子：
--
通讯作者：
Hardy RW
中科院分区：
文献类型：
--
作者：
Crawford JM;Yan LL;Zaher H;Hardy RW
为了在脊椎动物和蚊子宿主之间复制和传播，甲病毒必须与两种不同的宿主环境有效地相互作用。已知病毒颗粒组成中某些依赖宿主来源的差异似乎有助于传播周期。然而，宿主介导的包装病毒基因组RNA修饰对随后感染的影响尚未被研究过。在人类（HEK-293）细胞中，蚊子衍生的Sindbis病毒（SINV）复制和传播速度更快，产生的病毒比哺乳动物衍生的Sindbis病毒更具传染性。这种增强的复制既不是稳定性差异的结果，也不是感染基因组RNA产生的结果。然而，从蚊子来源的SINV纯化的基因组RNA比从哺乳动物来源的SINV纯化的基因组RNA更有效地在HEK-293细胞中建立感染，这表明基因组RNA本身在两个产生宿主之间是不同的，这种差异是感染的决定因素。与这一观点一致，我们发现蚊子衍生的SINV基因组RNA比哺乳动物衍生的SINV基因组RNA是一个更活跃的翻译模板，我们将这种差异归因于宿主对包装基因组RNA修饰的依赖变化，这是通过LC/MS-MS确定的。我们的数据支持这样的假设，即在其他因素中，包装的vRNA的宿主依赖性修饰谱可能在哺乳动物细胞中SINV感染和复制的效率中发挥重要作用。
Alphaviruses must interact efficiently with two distinct host environments in order to replicate and transmit between vertebrate and mosquito hosts. Some host-origin-dependent differences in virus particle composition that appear to facilitate the transmission cycle are known. However, the impact of host-mediated modification of packaged viral genomic RNA on subsequent infection has not been previously investigated. Here we show that in human (HEK-293) cells, mosquito-derived Sindbis virus (SINV) replicates and spreads faster, producing a more infectious virus than its mammalian-derived counterpart. This enhanced replication is neither a result of differences in the stability nor the production of the infecting genomic RNA. Nevertheless, purified genomic RNA from mosquito-derived SINV established infection in HEK-293 cells more efficiently than that of mammalian-derived SINV, indicating that the genomic RNA itself is different between the two producing hosts and this difference is a determinant of infection. In agreement with this idea, we show that mosquito-derived SINV genomic RNA is a more active template for translation than mammalian-derived SINV genomic RNA, and we attribute this difference to host-dependent changes in modification of packaged genomic RNA as determined by LC/MS-MS. Our data support the hypothesis that among other factors, the host-dependent modification profile of the packaged vRNA is likely to play an important role in the efficiency of SINV infection and replication in mammalian cells.
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