Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia.
Laboratory for Advanced Genomics, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Viruses. 2022 Jul 28;14(8):1661. doi: 10.3390/v14081661.
Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182, are reproducibly deregulated during productive infection. These miRNAs are predicted to regulate a great number of potential targets involved in different cellular processes and have only 33 shared targets. Among these, members of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover, these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.
单纯疱疹病毒 1（HSV-1）表达大量的 microRNAs，但其功能尚不完全清楚。此外，已经发现 HSV-1 会使宿主 microRNAs 失调，这增加了病毒有效复制的调控的复杂性。在这项研究中，我们通过大规模平行测序全面研究了宿主 microRNAs 的失调。我们发现，只有来自单个簇的 microRNAs，miR-183/96/182，在有性感染期间被反复失调。这些 microRNAs 被预测可调节大量涉及不同细胞过程的潜在靶标，且仅有 33 个共享靶标。其中，FoxO 蛋白家族的成员被确定为这三种 microRNAs 的潜在靶标。然而，我们的研究表明，上调的 microRNAs 并不影响 FoxO 蛋白的表达，此外，这些蛋白在 HSV-1 感染中上调。此外，我们表明单个 FoxO 蛋白对于 HSV-1 的有效复制并非必需。总之，我们的结果表明，受感染细胞对病毒感染的反应复杂且冗余，而病毒则能有效地抑制这种反应。
