Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection.
Murine Polyomavirus encodes a microRNA that cleaves early RNA transcripts but is not essential for experimental infection.
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DOI：
10.1016/j.virol.2009.02.017
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发表时间：
2009-04-25
期刊：
影响因子：
3.7
通讯作者：
Ganem, Don
中科院分区：
文献类型：
--
作者：
Sullivan, Christopher S.;Sung, Chang K.;Pack, Christopher D.;Grundhoff, Adam;Lukacher, Aron E.;Benjamin, Thomas L.;Ganem, Don
MicroRNA是转录后调节基因表达的小调控RNA，可由病毒和细胞基因组编码。大多数病毒miRNAs的功能是未知的，并且很少在体内环境中进行研究。在这里，我们表明，鼠多瘤病毒（PyV）编码的前体microRNA被加工成两个成熟的microRNA，这两个都是积极的指导裂解的早期PyV的mRNA。此外，我们确定了一个缺失突变的多瘤病毒是有缺陷的编码microRNA。该突变体复制正常，转化培养细胞的效率与野生型PyV相当。miRNA突变体能够在肠胃外接种后建立小鼠的瞬时感染，并且在感染后以与野生型病毒大致相同的速率被清除。此外，在这些实验室条件下，我们观察到抗病毒CD8 T细胞应答无差异。这些结果表明，PyV的miRNA表达是不是培养细胞或实验接种的小鼠感染所必需的，并提高了其在自然感染中的作用可能涉及的收购或传播方面，而不是由实验接种重演的可能性。
MicroRNAs are small regulatory RNAs that post-transcriptionally regulate gene expression and can be encoded by viral as well as cellular genomes. The functions of most viral miRNAs are unknown and few have been studied in an in vivo context. Here we show that the murine polyomavirus (PyV) encodes a precursor microRNA that is processed into two mature microRNAs, both of which are active at directing the cleavage of the early PyV mRNAs. Furthermore, we identify a deletion mutant of polyomavirus that is defective in encoding the microRNAs. This mutant replicates normally and transforms cultured cells with efficiencies comparable to wildtype PyV. The miRNA mutant is competent to establish a transient infection of mice following parenteral inoculation, and is cleared post infection at approximately the same rate as the wildtype virus. In addition, under these laboratory conditions, we observe no differences in anti-viral CD8 T cell responses. These results indicate that PyV miRNA expression is not essential for infection of cultured cells or experimentally inoculated mice, and raise the possibility that its role in natural infection might involve aspects of acquisition or spread that are not recapitulated by experimental inoculation.
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