Abstract
Given the propensity of viruses to co-opt cellular pathways and activities for their benefit, it is perhaps not surprising that several viruses have now been shown to reshape the cellular environment by reprogramming the host's RNA-interference machinery. In particular, microRNAs are produced by the various members of the herpesvirus family during both the latent stage of the viral life cycle and the lytic (or productive) stage. Emerging data suggest that viral microRNAs are particularly important for regulating the transition from latent to lytic replication and for attenuating antiviral immune responses.
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References
Pfeffer, S. et al. Identification of virus-encoded microRNAs. Science 304, 734–736 (2004).
Cai, X. et al. Epstein–Barr virus microRNAs are evolutionarily conserved and differentially expressed. PLoS Pathog. 2, e23 (2006).
Grundhoff, A., Sullivan, C. S. & Ganem, D. A combined computational and microarray-based approach identifies novel microRNAs encoded by human γ-herpesviruses. RNA 12, 733–750 (2006).
Cai, X. et al. Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc. Natl Acad. Sci. USA 102, 5570–5575 (2005). This paper showed that viral miRNAs might be conserved during viral evolution.
Pfeffer, S. et al. Identification of microRNAs of the herpesvirus family. Nature Methods 2, 269–276 (2005). This paper documented the generation of miRNAs by several herpesvirus species.
Grey, F. et al. Identification and characterization of human cytomegalovirus-encoded microRNAs. J. Virol. 79, 12095–12099 (2005).
Cui, C. et al. Prediction and identification of herpes simplex virus 1-encoded microRNAs. J. Virol. 80, 5499–5508 (2006).
Umbach, J. L. et al. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 454, 780–783 (2008).
Schäfer, A., Cai, X., Bilello, J. P., Desrosiers, R. C. & Cullen, B. R. Cloning and analysis of microRNAs encoded by the primate γ-herpesvirus rhesus monkey rhadinovirus. Virology 364, 21–27 (2007).
Buck, A. H. et al. Discrete clusters of virus-encoded microRNAs are associated with complementary strands of the genome and the 7.2-kilobase stable intron in murine cytomegalovirus. J. Virol. 81, 13761–13770 (2007).
Dölken, L. et al. Mouse cytomegalovirus microRNAs dominate the cellular small RNA profile during lytic infection and show features of posttranscriptional regulation. J. Virol. 81, 13771–13782 (2007).
Yao, Y. et al. Marek's disease virus type 2 (MDV-2)-encoded microRNAs show no sequence conservation with those encoded by MDV-1. J. Virol. 81, 7164–7170 (2007).
Burnside, J. et al. Marek's disease virus encodes microRNAs that map to meq and the latency-associated transcript. J. Virol. 80, 8778–8786 (2006).
Sullivan, C. S., Grundhoff, A. T., Tevethia, S., Pipas, J. M. & Ganem, D. SV40-encoded microRNAs regulate viral gene expression and reduce susceptibility to cytotoxic T cells. Nature 435, 682–686 (2005). This paper described the first viral miRNA phenotype in culture.
Seo, G. J., Fink, L. H., O'Hara, B., Atwood, W. J. & Sullivan, C. S. Evolutionarily conserved function of a viral microRNA. J. Virol. 82, 9823–9828 (2008).
Xu, N., Segerman, B., Zhou, X. & Akusjarvi, G. Adenovirus virus-associated RNAII-derived small RNAs are efficiently incorporated into the RNA-induced silencing complex and associate with polyribosomes. J. Virol. 81, 10540–10549 (2007).
Lin, J. & Cullen, B. R. Analysis of the interaction of primate retroviruses with the human RNA interference machinery. J. Virol. 81, 12218–12226 (2007).
Ouellet, D. L. et al. Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element. Nucleic Acids Res. 36, 2353–2365 (2008).
Bartel, D. P. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004).
Murphy, E., Vanicek, J., Robins, H., Shenk, T. & Levine, A. J. Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc. Natl Acad. Sci. USA 105, 5453–5458 (2008).
Gottwein, E., Cai, X. & Cullen, B. R. Expression and function of microRNAs encoded by Kaposi's sarcoma-associated herpesvirus. Cold Spring Harb. Symp. Quant. Biol. 71, 357–364 (2006).
Barth, S. et al. Epstein–Barr virus-encoded microRNA miR-BART2 down-regulates the viral DNA polymerase BALF5. Nucleic Acids Res. 36, 666–675 (2008).
Hussain, M., Taft, R. J. & Asgari, S. An insect virus-encoded microRNA regulates viral replication. J. Virol. 82, 9164–9170 (2008).
Tang, S. et al. An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor. Proc. Natl Acad. Sci. USA 105, 10931–10936 (2008).
Wu, L., Fan, J. & Belasco, J. G. Importance of translation and nonnucleolytic Ago proteins for on-target RNA interference. Curr. Biol. 18, 1327–1332 (2008).
Brodersen, P. et al. Widespread translational inhibition by plant miRNAs and siRNAs. Science 320, 1185–1190 (2008).
He, B., Gross, M. & Roizman, B. The γ134.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc. Natl Acad. Sci. USA 94, 843–848 (1997).
Orvedahl, A. et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1, 23–35 (2007).
Grey, F., Meyers, H., White, E. A., Spector, D. H. & Nelson, J. A human cytomegalovirus-encoded microRNA regulates expression of multiple viral genes involved in replication. PLoS Pathog. 3, e163 (2007).
Lo, A. K. et al. Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Natl Acad. Sci. USA 104, 16164–16169 (2007).
Grey, F. & Nelson, J. Identification and function of human cytomegalovirus microRNAs. J. Clin. Virol. 41, 186–191 (2008).
Skalsky, R. L. et al. Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155. J. Virol. 81, 12836–12845 (2007).
Gottwein, E. et al. A viral microRNA functions as an ortholog of cellular miR-155. Nature 450, 1096–1099 (2007).
Zhao, Y. et al. A functional microRNA-155 ortholog encoded by the oncogenic Marek's disease virus. J. Virol. 83, 489–492 (2009).
Yin, Q. et al. MicroRNA-155 is an Epstein–Barr virus-induced gene that modulates Epstein–Barr virus-regulated gene expression pathways. J. Virol. 82, 5295–5306 (2008).
Samols, M. A. et al. Identification of cellular genes targeted by KSHV-encoded microRNAs. PLoS Pathog. 3, e65 (2007).
Stern-Ginossar, N. et al. Host immune system gene targeting by a viral miRNA. Science 317, 376–381 (2007).
Stern-Ginossar, N. et al. Human microRNAs regulate stress-induced immune responses mediated by the receptor NKG2D. Nature Immunol. 9, 1065–1073 (2008).
Choy, E. Y. et al. An Epstein–Barr virus-encoded microRNA targets PUMA to promote host cell survival. J. Exp. Med. 205, 2551–2560 (2008).
Xia, T. et al. EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res. 68, 1436–1442 (2008).
Acknowledgements
Work in my laboratory was supported by the National Institutes of Health (grant numbers GM071408 and AI067968). I thank M. Luftig, E. Gottwein and J. L. Umbach for critical comments on the manuscript.
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Correspondence should be addressed to the author (culle002@mc.duke.edu).
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Cullen, B. Viral and cellular messenger RNA targets of viral microRNAs. Nature 457, 421–425 (2009). https://doi.org/10.1038/nature07757
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DOI: https://doi.org/10.1038/nature07757
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