SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells
SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells
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DOI：
10.1038/nature03576
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发表时间：
2005-06-02
期刊：
影响因子：
64.8
通讯作者：
Ganem, D
中科院分区：
文献类型：
--
作者：
Sullivan, CS;Grundhoff, AT;Ganem, D
MicroRNA (miRNA) 是一种小型（类似于 22 个核苷酸）RNA，在低等生物体中，通常通过与目标信使 RNA 形成不完美的双链体，在发育和基因表达中发挥重要的调节作用。哺乳动物细胞和 Epstein-Barr 病毒 (EBV) 感染中也有 miRNA 的描述，但其中大多数的功能尚不清楚。尽管一种 EBV miRNA 可能改变了病毒 mRNA 的加工 (2)，但这一事件的调控意义尚不确定，因为存在其他可以提供目标功能的转录本 (3)。在这里，我们报告了由猿猴病毒 40 (SV40) 编码的 miRNA 的鉴定，并定义了它们对病毒感染的功能意义。 SVmiRNA 在感染后期积累，与早期病毒 mRNA 完美互补，并以这些 mRNA 为目标进行切割。这减少了病毒 T 抗原的表达，但相对于缺乏 SVmiRNA 的突变体产生的感染性病毒的产量，并没有减少感染性病毒的产量。然而，野生型 SV40 感染的细胞对细胞毒性 T 细胞裂解的敏感性低于突变型细胞，并且引发此类细胞产生较少的细胞因子。因此，病毒进化利用 miRNA 途径来产生效应子，从而提高成功感染的可能性。
MicroRNAs ( miRNAs) are small (similar to 22-nucleotide) RNAs that in lower organisms serve important regulatory roles in development and gene expression, typically by forming imperfect duplexes with target messenger RNAs1. miRNAs have also been described in mammalian cells and in infections with Epstein - Barr virus (EBV), but the function of most of them is unknown. Although one EBV miRNA probably altered the processing of a viral mRNA(2), the regulatory significance of this event is uncertain, because other transcripts exist that can supply the targeted function(3). Here we report the identification of miRNAs encoded by simian virus 40 (SV40) and define their functional significance for viral infection. SVmiRNAs accumulate at late times in infection, are perfectly complementary to early viral mRNAs, and target those mRNAs for cleavage. This reduces the expression of viral T antigens but does not reduce the yield of infectious virus relative to that generated by a mutant lacking SVmiRNAs. However, wild-type SV40-infected cells are less sensitive than the mutant to lysis by cytotoxic T cells, and trigger less cytokine production by such cells. Thus, viral evolution has taken advantage of the miRNA pathway to generate effectors that enhance the probability of successful infection.