Competitive virus and host RNAs: the interplay of a hidden virus and host interaction

Abstract

During virus infection, viral RNAs and mRNAs function as blueprints for viral protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs) in innate immunity. Here, considering recent research progress in microRNAs (miRNAs) and competitive endogenous RNAs (ceRNAs), we speculate that viral RNAs act as sponges and can sequester endogenous miRNAs within infected cells, thus cross-regulating the stability and translational efficiency of host mRNAs with shared miRNA response elements. This cross-talk and these reciprocal interactions between viral RNAs and host mRNAs are termed “competitive viral and host RNAs” (cvhRNAs). We further provide recent experimental evidence for the existence of cvhRNAs networks in hepatitis B virus (HBV), as well as Herpesvirus saimiri (HVS), lytic murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) infections. In addition, the cvhRNA hypothesis also predicts possible cross-regulation between host and other viruses, such as hepatitis C virus (HCV), HIV, influenza virus, human papillomaviruses (HPV). Since the interaction between miRNAs and viral RNAs also inevitably leads to repression of viral RNA function, we speculate that virus may evolve either to employ cvhRNA networks or to avoid miRNA targeting for optimal fitness within the host. CvhRNA networks may therefore play a fundamental role in the regulation of viral replication, infection establishment, and viral pathogenesis.

Keywords

cvhRNAs / virus RNAs / host mRNAs / miRNA response element / ceRNAs

References

[1] Ala U, Karreth FA, Bosia C, Pagnani A, Taulli R, Léopold V, Tay Y, Provero P, Zecchina R, Pandolfi PP (2013) Integrated transcriptional and competitive endogenous RNA networks are crossregulated in permissive molecular environments. Proc Natl Acad Sci USA110: 7154-7159

[2] Augui S, Nora EP, Heard E (2011) Regulation of X-chromosome inactivation by the X-inactivation centre. Nat Rev Genet12: 429-442

[3] Carl JW Jr, Trgovcich J, Hannenhalli S (2013) Widespread evidence of viral miRNAs targeting host pathways. BMC Bioinf14(Suppl 2): S3

[4] Cazalla D, Yario T, Steitz JA (2010) Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA.Science328: 1563-1566

[5] Dabrowska A, Kim N, Aldovini A (2008) Tat-induced FOXO3a is a key mediator of apoptosis in HIV-1-infected human CD4+ T lymphocytes. J Immunol181: 8460-8477

[6] Fang L, Du WW, Yang X, Chen K, Ghanekar A, Levy G, Yang W, Yee AJ, Lu WY, Xuan JW (2013) Versican 3′-untranslated region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity. FASEB J27: 907-919

[7] Filipowicz W, Grosshans H (2011) The liver-specific microRNA miR-122: biology and therapeutic potential. Prog Drug Res67: 221-238

[8] Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, Mussolin L, Ruggero K, Bonanno L, Guffanti A (2011) Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood117: 7053-7062

[9] Goubau D, Deddouche S, Reis E, Sousa C (2013) Cytosolic sensing of viruses. Immunity38: 855-869

[10] Gunasekharan V, Laimins LA (2013) Human papillomaviruses modulate microRNA 145 expression to directly control genome amplification. J Virol87: 6037-6043

[11] Hao J, Jin W, Li X, Wang S, Zhang X, Fan H, Li C, Chen L, Gao B, Liu G (2013) Inhibition of alpha interferon (IFN-α)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-α. J Virol87: 137-147

[12] Hu J, Xu Y, Hao J, Wang S, Li C, Meng S (2012) MiR-122 in hepatic function and liver diseases. Protein Cell3: 364-371

[13] Huang J, Wang F, Argyris E, Chen K, Liang Z, Tian H, Huang W, Squires K, Verlinghieri G, Zhang H (2007) Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med13: 1241-1247

[14] Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science309: 1577-1581

[15] Karreth FA, Pandolfi PP (2013) ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov3: 1113-1121

[16] Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA (2011) In vivo identification of tumor-suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell147: 382-395

[17] Kincaid RP, Sullivan CS (2012) Virus-encoded microRNAs: an overview and a look to the future. PLoS Pathog8: e1003018

[18] Klase Z, Houzet L, Jeang KT (2012) MicroRNAs and HIV-1: complex interactions. J Biol Chem287: 40884-40890

[19] Kong G, Zhang J, Zhang S, Shan C, Ye L, Zhang X (2011) Upregulated microRNA-29a by hepatitis B virus X protein enhances hepatoma cell migration by targeting PTEN in cell culture model. PLoS ONE6: e19518

[20] Lee S, Song J, Kim S, Kim J, Hong Y, Kim Y, Kim D, Baek D, Ahn K (2013a) Selective degradation of host MicroRNAs by an intergenic HCMV noncoding RNA accelerates virus production. Cell Host Microbe13: 678-690

[21] Lee YH, Lai CL, Hsieh SH, Shieh CC, Huang LM, Wu-Hsieh BA (2013b) Influenza A virus induction of oxidative stress and MMP-9 is associated with severe lung pathology in a mouse model. Virus Res178: 411-422

[22] Li C, Wang Y, Wang S, Wu B, Hao J, Fan H, Ju Y, Ding Y, Chen L, Chu X (2013) HBV mRNAs-mediated miR-122 inhibition up-regulates PTTG1-binding protein which promotes HCC tumor growth and cell invasion. J Virol87: 2193-2205

[23] Ling S, Birnbaum Y, Nanhwan MK, Thomas B, Bajaj M, Li Y, Li Y, Ye Y (2013a) Dickkopf-1 (DKK1) phosphatase and tensin homolog on chromosome 10 (PTEN) crosstalk via microRNA interference in the diabetic heart. Basic Res Cardiol108: 352

[24] Ling S, Birnbaum Y, Nanhwan MK, Thomas B, Bajaj M, Ye Y (2013b) MicroRNA-dependent cross-talk between VEGF and HIF1α in the diabetic retina. Cell Signal25: 2840-2847

[25] Liu N, Zhang J, Jiao T, Li Z, Peng J, Cuizhu Q, Ye X (2013) Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging miR-15a/16 cluster. J Virol87: 13370-13378

[26] Manigold T, Racanelli V (2007) T-cell regulation by CD4 regulatory T cells during hepatitis B and C virus infections: facts and controversies. Lancet Infect Dis7: 804-813

[27] Marcinowski L, Tanguy M, Krmpotic A, Rädle B, Lisnić VJ,Tuddenham L, Chane-Woon-Ming B, Ruzsics Z, Erhard F, Benkartek C (2012) Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo. PLoS Pathog8: e1002510

[28] Miyoshi K, Okada TN, Siomi H, Siomi MC (2009) Characterization of the miRNA-RISC loading complex and miRNA-RISC formed in the Drosophila miRNA pathway. RNA15: 1282-1291

[29] Newman MA, Hammond SM (2010) Emerging paradigms of regulated microRNA processing. Genes Dev24: 1086-1092

[30] Noorbakhsh J, Lang AH, Mehta P (2013) Intrinsic noise of microRNAregulated genes andthe ceRNA hypothesis. PLoS ONE8: e72676

[31] Pang PS, Pham EA, Elazar M, Patel SG, Eckart MR, Glenn JS (2012) Structural map of a Pan PS, microRNA-122: hepatitis C virus complex. J Virol86: 1250-1254

[32] Poliseno L, Salmena L, Zhang J, Carver B, Haveman WJ, Pandolfi PP (2010) A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature465: 1033-1038

[33] Redman TK, Brittm WJ,Wilcox CM, Graham MF, Smith PD (2002) Human cytomegalovirus enhances chemokine production by lipopolysaccharide-stimulated lamina propria macrophages. J Infect Dis185: 584-590

[34] Shan Y, Zheng J, Lambrecht RW, Bonkovsky HL (2007) Reciprocal effects of micro-RNA-122 on expression of heme oxygenase-1 and hepatitis C virus genes in human hepatocytes. Gastroenterology133: 1166-1174

[35] Sharma M, Callen S, Zhang D, Singhal PC, Vanden Heuvel GB, Buch S (2010) Activation of Notch signaling pathway in HIVassociated nephropathy. AIDS24: 2161-2170

[36] Shimakami T, Yamane D, Jangra RK, Kempf BJ, Spaniel C, Barton DJ, Lemon SM (2012) Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proc Natl Acad Sci USA109: 941-946

[37] Song L, Liu H, Gao S, Jiang W, Huang W (2010) Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol84: 8849-8860

[38] Sun G, Li H, Wu X, Covarrubias M, Scherer<?Pub Caret?> L, Meinking K, Luk B, Chomchan P, Alluin J, Gombart AF (2012) Interplay between HIV-1 infection and host microRNAs. Nucleic Acids Res40: 2181-2196

[39] Swaminathan S, Zaunders J, Wilkinson J, Suzuki K, Kelleher AD (2009) Does the presence of anti-HIV miRNAs in monocytes explain their resistance to HIV-1 infection? Blood113: 5029-5030

[40] Szabó J, Bácsi A, Beck Z, Kiss J, Andirkó I, Tóth FD (1999) Role of interleukin-8 and transforming growth factor-beta1 in enhancement of human cytomegalovirus replication by human T cell leukemia-lymphoma virus type I in macrophages co-infected with both viruses. J Interferon Cytokine Res19: 209-217

[41] Tang-Feldman YJ, Lochhead SR, Lochhead GR, Yu C, George M, Villablanca AC, Pomeroy C (2013) Murine cytomegalovirus (MCMV) infection upregulates P38 MAP kinase in aortas of Apo E KO mice: a molecular mechanism for MCMV-induced acceleration of atherosclerosis. J Cardiovasc Transl Res6: 54-64

[42] Torres AG, Fabani MM, Vigorito E, Gait MJ (2011) MicroRNA fate upon targeting with anti-miRNA oligonucleotides as revealed by an improved Northern-blot-based method for miRNA detection. RNA17: 933-943

[43] Ulitsky I, Bartel DP (2013) lincRNAs: genomics, evolution, and mechanisms. Cell154: 26-46

[44] Wang S, Qiu L, Yan X, Jin W, Wang Y, Chen L, Wu E, Ye X, Gao GF, Wang F (2012) Loss of MiR-122 expression in patients with hepatitis B enhances hepatitis B virus replication through cyclin G1 modulated P53 activity. Hepatology55: 730-741

[45] Wang S, Zhang X, Ju Y, Zhao B, Yan X, Hu J, Shi L, Yang L, Ma Z, Chen L (2013a) MicroRNA-146a feedback suppresses Tcell immune function by targeting Stat1 in patients with chronic hepatitis B. J Immunol191: 293-300

[46] Wang Y, Jiang L, Ji X, Yang B, Zhang Y, Fu XD (2013b) Hepatitis B viral RNA directly mediates down-regulation of the tumor suppressor microRNA miR-15a/miR-16-1 in hepatocytes. J Biol Chem288: 18484-18493

[47] Yu Z, Willmarth NE, Zhou J, Katiyar S, Wang M, Liu Y, McCue PA, Quong AA, Lisanti MP, Pestell RG (2010) microRNA 17/20 inhibits cellular invasion and tumor metastasis in breast cancer by heterotypic signaling. Proc Natl Acad Sci USA107: 8231-8236

[48] Yuan M, Zhan Q, Duan X, Song B, Zeng S, Chen X, Yang Q, Xia J (2013) A functional polymorphism at miR-491-5p binding site in the 3′-UTR of MMP-9 gene confers increased risk for atherosclerotic cerebral infarction in a Chinese population. Atherosclerosis226: 447-452

[49] Zhang X, Hou J, Lu M (2013) Regulation of hepatitis B virus replication by epigenetic mechanisms and microRNAs.Front Genet4: 202

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