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Non-coding Regulatory RNAs of the DNA Tumor Viruses

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DNA Tumor Viruses

Abstract

Viral non-coding RNAs (ncRNAs) exist in various forms, many of which appear unique to a particular DNA tumor virus family. In contrast, virally encoded microRNAs (miRNAs) represent a strategy used by several DNA tumor virus families to tap into the same processing and effector machinery utilized by host-derived miRNAs. Whether encoded during latent or lytic infection, ncRNAs are often among the most highly expressed viral transcripts, implying that they have important functions in the viral life cycle. Viral ncRNAs have been shown to contribute to viral gene autoregulation, modification of the host cell apoptotic response, and enhance the translation of viral proteins. While our knowledge of the various viral ncRNAs continues to grow, there remain surprising gaps in our understanding of the functions of some viral ncRNAs, especially given their abundance and the fact that they were discovered decades ago. Here, we provide an overview of the current understanding of the regulatory ncRNAs encoded by the DNA tumor viruses, including the VA RNAs, EBERs, HSURs, PAN, and the recently discovered viral miRNAs.

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Acknowledgments

Work in CSS lab is funded by UT Austin start up funds & a Fellowship from the UT Austin Institute for Cellular and Molecular Biology. Research into viral miRNA function in the Cullen laboratory is supported by NIH Grant AI067968. We thank Dr. Joan Steitz and Latham Fink for helpful comments regarding this chapter, and Jennifer Lin, Xuezhong Cai, Eva Gottwein, and Latham Fink for help with the figures. The manuscript proposing the existence of a miRNA called miR-LAT within the LAT transcripts of HSV-1 (Gupta et al., 2006) has now been retracted. A recent manuscript (Umbach, J. L., Kramer, M. F., Jurak, I., Coen, D. M., & Cullen, B. R. 2008, MicroRNAs expressed by Herpes Simplex Virus 1 during latent neuronal infection regulate viral gene expression. Nature, 454, 780–783) has now reported that HSV-1 LAT is processed to give rise to four viral miRNAs, miR-H2 to miR-H5, while an additional HSV-1 miRNA, miR-H6, was found to be encoded outside LAT. All five HSV-1 miRNA were found to be expressed in latently infected neurons in vivo. Moreover, miR-H2 and miR-H6 were found to inhibit expression of the HSV-1 immediate early transcription factors ICP-0 and ICP-4 respectively. This suggests that these viral miRNA may stabilize HSV-1 latency in infected neurons in vivo.

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  1. The University of Texas at Austin,Molecular Genetics and Microbiology, 1 University Station A5000, Austin, TX 78712-0162, USA

    Christopher S. Sullivan

  2. Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA

    Bryan R. Cullen

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  1. Christopher S. Sullivan
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Correspondence to Christopher S. Sullivan or Bryan R. Cullen .

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  1. University of North Carolina Chapel Hill, NC, USA

    Blossom Damania

  2. University of Pittsburgh Pittsburgh, PA, USA

    James M. Pipas

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Sullivan, C.S., Cullen, B.R. (2009). Non-coding Regulatory RNAs of the DNA Tumor Viruses. In: Damania, B., Pipas, J.M. (eds) DNA Tumor Viruses. Springer, New York, NY. https://doi.org/10.1007/978-0-387-68945-6_25

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