**Author details**

Venugopal Nair and Yongxiu Yao\* The Pirbright Institute and UK-China Centre of Excellence for Research on Avian Diseases, Surrey, United Kingdom

\*Address all correspondence to: yongxiu.yao@pirbright.ac.uk

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**43**

*Role of Virus-Encoded microRNAs in Avian Viral Diseases*

with the human rna interference machinery. Journal of Virology.

[11] Yao Y, Smith LP, Nair V, Watson M. An avian retrovirus uses canonical expression and processing mechanisms to generate viral microrna. Journal of

[12] Kincaid RP, Burke JM, Sullivan CS. Rna virus microrna that mimics a b-cell oncomir. Proceedings of the National Academy of Sciences of the United States of America.

[13] Rosewick N, Momont M, Durkin K, Takeda H, Caiment F, Cleuter Y, et al. Deep sequencing reveals abundant noncanonical retroviral micrornas in b-cell leukemia/lymphoma. Proceedings of the National Academy of Sciences of the United States of America.

[14] Legione AR, Coppo MJ, Lee SW, Noormohammadi AH, Hartley CA, Browning GF, et al. Safety and vaccine efficacy of a glycoprotein g deficient strain of infectious laryngotracheitis virus delivered in ovo. Vaccine.

[15] Morrow C, Fehler F. Marek's disease: A worldwide problem. In: Davison F, Nair V, editors. Marek's disease: An evolving problem. Oxford: Elsevier Academic Press; 2004. pp. 49-61

[16] Bublot M, Sharma J. Vaccination against marek's disease. In: Davison F, Nair V, editors. Marek's Disease, an Evolving Problem. Amsterdam: Elsevier Academic Press; 2004.

[17] Gimeno IM. Marek's disease vaccines: A solution for today but a worry for tomorrow? Vaccine. 2008;**26**(Suppl 3):C31-C41

2007;**81**:12218-12226

Virology. 2014;**88**(1):2-9

2012;**109**:3077-3082

2013;**110**:2306-2311

2012;**30**:7193-7198

pp. 168-185

*DOI: http://dx.doi.org/10.5772/intechopen.89688*

[1] Lee RC, Feinbaum RL, Ambros V. The *C. elegans* heterochronic gene lin-4 encodes small rnas with antisense complementarity to lin-14. Cell.

[2] Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed rnas. Science. 2001;**294**:853-858

[3] Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny rnas with probable regulatory roles in *Caenorhabditis elegans*. Science.

[4] Lee RC, Ambros V. An extensive class of small rnas in *Caenorhabditis elegans*.

1993;**75**:843-854

**References**

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2013;**9**:e1003694

2012;**8**:e1003018

Science. 2001;**294**:862-864

[5] Cullen BR. How do viruses avoid inhibition by endogenous cellular micrornas. PLoS Pathogens.

[6] Libri V, Miesen P, van Rij RP, Buck AH. Regulation of microrna biogenesis and turnover by animals and their viruses. Cellular and Molecular Life Sciences: CMLS. 2013;**70**:3525-3544

[7] Kincaid RP, Sullivan CS. Virusencoded micrornas: An overview and a look to the future. PLoS Pathogens.

[8] Chen CJ, Cox JE, Kincaid RP, Martinez A, Sullivan CS. Divergent microrna targetomes of closely related circulating strains of a polyomavirus. Journal of Virology. 2013;**87**:11135-11147

[9] Kincaid RP, Burke JM, Cox JC, de Villiers EM, Sullivan CS. A human torque Teno virus encodes a microrna that inhibits interferon signaling. PLoS

[10] Lin J, Cullen BR. Analysis of the interaction of primate retroviruses

Pathogens. 2013;**9**:e1003818

*Role of Virus-Encoded microRNAs in Avian Viral Diseases DOI: http://dx.doi.org/10.5772/intechopen.89688*

## **References**

*Non-Coding RNAs*

and pathogenesis.

**Acknowledgements**

**Conflict of interest**

**Author details**

Venugopal Nair and Yongxiu Yao\*

Diseases, Surrey, United Kingdom

provided the original work is properly cited.

The authors declare no conflict of interest.

and accurate target information of viral miRNAs although target identification using target prediction software provided an initial strategy. Several techniques such as RIP-CHIP (RNA-binding protein immunoprecipitation microarray), HITS-CLIP (high-throughput sequencing cross-linking and immunoprecipitation), PAR-CLIP and proteomics analysis have all contributed large amount of data on potential targets of virus-encoded miRNAs [47, 83–89] although only PAR-CLIP has been used for avian herpesvirus miRNA targetome identification [64]. Cross-linking, ligation and sequencing of hybrids (CLASH) technology, another biochemical screen for miRNA targets, promises to generate the most accurate target information to date, leading the way in the generation of high confidence target datasets which will be invaluable for future studies [90, 91]. These new technologies allow unprecedented and largely unbiased views into miRNAs-mediated regulation of gene expression in virus-infected cells. Undoubtedly, further studies using different approaches and technologies are required toward the clear definition of miRNAs targetome and their functional relevance in viral infection, latency, reactivation,

Authors would like to acknowledge the funding (BBS/E/I/00007032, BB/ R007896/1 and BB/R012865/1) from the Biotechnology and Biological Sciences Research Council (BBSRC) United Kingdom and BBSRC Newton Fund Joint Centre

The Pirbright Institute and UK-China Centre of Excellence for Research on Avian

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*Address all correspondence to: yongxiu.yao@pirbright.ac.uk

Awards on "UK-China Centre of Excellence for Research on Avian Diseases".

**42**

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[9] Kincaid RP, Burke JM, Cox JC, de Villiers EM, Sullivan CS. A human torque Teno virus encodes a microrna that inhibits interferon signaling. PLoS Pathogens. 2013;**9**:e1003818

[10] Lin J, Cullen BR. Analysis of the interaction of primate retroviruses

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Rasschaert D, et al. A p53-dependent promoter associated with polymorphic tandem repeats controls the expression of a viral transcript encoding clustered micrornas. RNA. 2010;**16**:2263-2276

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encoded micrornas show no sequence conservation with those encoded by mdv-1. Journal of Virology.

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Marek's disease virus encodes micrornas

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**44**

2008;**82**:4007-4015

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**49**

**Chapter 5**

**Abstract**

drial homeostasis.

**1. Introduction**

MicroRNAs in the Functional

*Fabien P. Chevalier, Julie Rorteau and Jérôme Lamartine*

Humankind has always been intrigued by death, as illustrated by the eternal quest for the fountain of youth. Aging is a relentless biological process slowly progressing as life cycle proceeds. Indeed, aging traduces an accumulation of physiological changes over time that render organisms more likely to die. Thus, despite our mastery of advanced technologies and robust medical knowledge, defining the molecular basis of aging to control lifespan is still currently one of the greatest challenges in biology. In mammals, the skin is the ultimate multitasker vital organ, protecting organisms from the world they live in. As a preferential interface with the environment, the skin is reflecting the internal physiological balances. The maintenance of these balances, called homeostasis, depends on the concurrent assimilation of diversified signals at the cellular level. MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression by mRNAs degradation or translational repression. Their relatively recent discovery in 2000 provided new insights into the understanding of the gene regulatory networks. In this chapter, we focused on the role of three miRNA families, namely miR-30, miR-200, and miR-181, playing a key role in the progression of the skin aging process, with particular input in mechanistic considerations related to autophagy, oxidative stress, and mitochon-

**Keywords:** skin, microRNA, epidermis, keratinocyte, fibroblast, aging, autophagy,

Skin, the largest vital organ in the body, is made of three distinct layers from the top to the depth: the epidermis, which is a fine layer of epithelial keratinized cells called keratinocytes; the dermis consisting of fibroblasts in an intracellular matrix with various additional structures such as hear follicles, sweat glands, nerve endings, and capillaries; and the profound subcutaneous tissue called hypodermis. As a physical barrier between the body and the environment, the skin is affected by both intrinsic and extrinsic aging. Intrinsic or chronological aging is a natural continuous dynamic process that normally begins in the mid-1920s. During this inexorable process, the skin undergoes a physiological deterioration characterized by skin atrophy, increased physical and immunological vulnerability, with a reduced capacity of tissue repair in case of wounding. More precisely, intrinsic aging is leading to a 10–50% thinning of the epidermis, the flattening of the dermal-epidermal junction, an atrophy of the dermis with disorganization of the collagen and elastic fibers, a reduction of the microvasculature, and a loose of adipose tissue [1]. The

oxidative stress, mitochondria, miR-30, miR-200, miR-181

Defects of Skin Aging

## **Chapter 5**

*Non-Coding RNAs*

2010;**10**:688-698

2015;**96**:637-649

[80] Dang L, Teng M, Li HZ, Ma SM, Lu QX, Hao HF, et al. Marek's disease virus type 1 encoded analog of mir-155 promotes proliferation of chicken embryo fibroblast and df-1 cells by targeting hnrnpab. Veterinary Microbiology. 2017;**207**:210-218

human micrornas co-target oncogenic and apoptotic viral and human genes during latency. The EMBO Journal.

[88] Skalsky RL, Corcoran DL, Gottwein E, Frank CL, Kang D, Hafner M, et al. The viral and cellular microrna targetome in lymphoblastoid

cell lines. PLoS Pathogens.

[89] Lee SH, Kalejta RF, Kerry J,

[90] Grosswendt S, Filipchyk A, Manzano M, Klironomos F,

Schilling M, Herzog M, et al. Unambiguous identification of mirna: Target site interactions by different types of ligation reactions. Molecular Cell.

[91] Helwak A, Kudla G, Dudnakova T, Tollervey D. Mapping the human mirna interactome by clash reveals frequent

[92] Yao Y, Nair V. Role of virus-encoded micrornas in avian viral diseases. Viruses. 2014;**6**:1379-1394

noncanonical binding. Cell.

Semmes OJ, O'Connor CM, Khan Z, et al. Bclaf1 restriction factor is neutralized by proteasomal degradation and microrna repression during human cytomegalovirus infection. Proceedings of the National Academy of Sciences of the United States of America.

2012;**31**:2207-2221

2012;**8**:e1002484

2012;**109**:9575-9580

2014;**54**:1042-1054

2013;**153**:654-665

[81] Kanneganti TD. Central roles of nlrs and inflammasomes in viral infection. Nature Reviews. Immunology.

[82] Teng M, Yu ZH, Sun AJ, Min YJ, Chi JQ, Zhao P, et al. The significance of the individual meq-clustered mirnas of marek's disease virus in oncogenesis. The Journal of General Virology.

[83] Dolken L, Malterer G, Erhard F, Kothe S, Friedel CC, Suffert G, et al. Systematic analysis of viral and cellular microrna targets in cells latently infected with human gamma-herpesviruses by risc immunoprecipitation assay. Cell Host & Microbe. 2010;**7**:324-334

[84] Gallaher AM, Das S, Xiao Z,

Andresson T, Kieffer-Kwon P, Happel C, et al. Proteomic screening of human targets of viral micrornas reveals functions associated with immune evasion and angiogenesis. PLoS Pathogens. 2013;**9**:e1003584

[85] Haecker I, Gay LA, Yang Y, Hu J, Morse AM, McIntyre LM, et al. Ago hits-clip expands understanding of kaposi's sarcoma-associated

herpesvirus mirna function in primary effusion lymphomas. PLoS Pathogens.

[86] Pavelin J, Reynolds N, Chiweshe S, Wu G, Tiribassi R, Grey F. Systematic microrna analysis identifies atp6v0c as an essential host factor for human cytomegalovirus replication. PLoS Pathogens. 2013;**9**:e1003820

[87] Riley KJ, Rabinowitz GS, Yario TA, Luna JM, Darnell RB, Steitz JA. Ebv and

2012;**8**:e1002884

**48**
