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		<title>AAVS_MH20150503150533_ Sahu AR et al</title>
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			<p class="Type-of-Article">&nbsp;</p>
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			<p class="Type-of-Article">Review Article</p>
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			<p class="title- ParaOverride-1">Host-Virus Interaction: Role of miRNA and Bioinformatics Tools for miRNA Target Prediction</p>
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			<p class="Authors ParaOverride-1">&nbsp;</p>
			<p class="Authors ParaOverride-1"><span class="CharOverride-1">Amit Ranjan Sahu</span><span class="CharOverride-2">1</span><span class="CharOverride-1">*, Sajad Ahmad Wani</span><span class="CharOverride-2">1</span><span class="CharOverride-1">, Arpita Padhy</span><span class="CharOverride-2">2</span><span class="CharOverride-1">, Amod Kumar</span><span class="CharOverride-2">3</span><span class="CharOverride-1">, </span><span class="CharOverride-1" xml:lang="en-US">Govindarajan</span><span class="CharOverride-1"> Bhuvana Priya</span><span class="CharOverride-2">4</span><span class="CharOverride-1">, Aditya Prasad Sahoo</span><span class="CharOverride-2">1</span><span class="CharOverride-1">, Ashok Kumar Tiwari</span><span class="CharOverride-2">5</span><span class="CharOverride-1">, Ravi Kumar Gandham</span><span class="CharOverride-2">1</span></p>
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			<p class="Affiliations ParaOverride-1"><span class="CharOverride-3">1</span>Computational Biology and Genomics Facility, Division of Veterinary Biotechnology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP-243122; <span class="CharOverride-3">2</span>Department of Veterinary Microbiology, Aarawali Veterinary College, Sikar, Rajasthan- 332001; <span class="CharOverride-3">3</span>Division of Animal Genetics; <span class="CharOverride-3">4</span>Division of Bacteriology and Mycology; <span class="CharOverride-3">5</span>Division of Standardization, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP-243122, India.</p>
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			<p class="Abstract">&nbsp;</p>
			<p class="Abstract"><span class="CharOverride-4">Abstract</span> | MicroRNAs (miRNAs) are the small endogenous regulatory non-coding RNAs of approximately 22 nucleotide lengths and are the players of post-transcriptional gene silencing in eukaryotes. miRNAs are the crucial factor in a diverse biological processes such as antiviral defence, oncogenesis and development in higher eukaryotes. When a virus encounters a host there is a complex network of interaction exist defining both host and virus. Though there is several class of factors or molecules involved in that interaction, the role of miRNAs cannot be ignored here. Host encodes its own miRNAs and virus does it’s too. Both the systems work for their own benefits. From this crosstalk we can deduce four relationships between the miRNAs of both host and virus for our better understanding. These are host encoded miRNAs interact with host as well as virus and similar interaction can be for viral miRNAs too. The investigation of this complex relationship deduces some of the important points regarding the molecular pathogenesis of the virus and opens a wide path for the suitable strategy to combat the ill effect of the virus. At present several bioinformatics tools are available for the prediction of miRNAs and its target sequence through suitable algorithms pertaining to their own method. So in a vast of whole genome data, miRNA and its target identification is no longer a tedious job. This review focuses on the complete interactions between host and viruses and several bioinformatics tools available with us for its interpretation. </p>
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			<p class="Abstract"><span class="CharOverride-4">Keywords</span> | microRNA, Non-regulatory RNAs, Post-transcriptional gene silencing, Antiviral defense, Oncogenesis</p>
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			<p class="Editor----Citation"><span class="CharOverride-4">Editor</span> | Muhammad Munir (DVM, PhD), Avian Viral Diseases Program, Compton Laboratory, Newbury, Berkshire, RG20 7NN, United Kingdom.</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Received</span> | May 03, 2015; <span class="CharOverride-4">Revised</span> | May 20, 2015; <span class="CharOverride-4">Accepted</span> | May 21, 2015; <span class="CharOverride-4">Published</span> | May 24, 2015&#9;&#9;</p>
			<p class="Editor----Citation"><span class="CharOverride-4">*Correspondence</span> | Amit Ranjan Sahu, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, UP, India; <span class="CharOverride-4">Email:</span> dramitr.sahu@gmail.com</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Citation</span> | Sahu AR, Wani SA, Padhy A, Kumar A, Priya GB, Sahoo AP, Tiwari AK, Gandham RK (2015). Host-virus interaction: role of miRNA and bioinformatics tools for miRNA target prediction. Adv. Anim. Vet. Sci. 3(4s): 30-36.  </p>
			<p class="Editor----Citation"><span class="CharOverride-4">DOI</span> | <a href="http://dx.doi.org/10.14737/journal.aavs/2015/3.4s.30.36"><span class="Hyperlink">http://dx.doi.org/10.14737/journal.aavs/2015/3.4s.30.36</span></a></p>
			<p class="Editor----Citation"><span class="Editor---Citation CharOverride-4">ISSN (Online)</span> | 2307-8316; <span class="Editor---Citation CharOverride-4">ISSN (Print)</span> | 2309-3331</p>
			<p class="Editor----Citation"><span class="CharOverride-4">Copyright</span> © 2015 Sahu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p>
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			<p class="Heading-1--Introduction----">&nbsp;</p>
		  <p class="Heading-1--Introduction----">INTRODUCTION</p>
			<p class="Caps-on-First-Para ParaOverride-1">&nbsp;</p>
			<p class="Caps-on-First-Para ParaOverride-1"><span class="_idGenDropcap-1">M</span><span>icroRNAs </span>(miRNAs or miRs) are the small, non-coding, regulatory, functional and endogenously produced RNA molecules of approximately 22 nucleotide in length and mediate gene expression post-transcriptionally (<a href="#Scaria-V--Hariharan-M--et-al.--2007"><span class="Hyperlink">Scaria et al., 2007</span></a>; <a href="#Bartel-DP--2004"><span class="Hyperlink">Bartel, 2004</span></a>; <a href="#Sullivan-CS--Ganem-D--2005-"><span class="Hyperlink">Sullivan et al., 2005</span></a>; <a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>; <a href="#Srinivasan-S--Selvan-ST--Archunan-G--Gulyas-B--Padmanabhan-P--2013"><span class="Hyperlink">Srinivasan et al., 2013</span></a>). Initially discovered in <span class="CharOverride-6">C. elegans</span> and now widely distributed through several strata of taxonomy (<a href="#Ghosh-Z--Mallick-B--Chakrabarti-J--2009"><span class="Hyperlink">Ghosh et al., 2009</span></a>). The miRBase is an online database that contains published microRNA sequences data and its annotation.  The latest release of miRBase is Release 21 which contains 28645 hairpin structured precursor miRNAs, 35828 nos. mature miRNAs in 223 different species (<a href="#Griffiths-Jones-S--Saini-HK--Dongen-SV--Enright-AJ--2008"><span class="Hyperlink">Griffiths-Jones et al., 2008</span></a>; <a href="#Kozomara-A--Griffiths-Jones-S--2014-"><span class="Hyperlink">Kozomora et al., 2014</span></a>). miRNAs are the key regulators of several biological processes, gene expression pattern and biomarker for diseases (<a href="#Pritchard-CC--Cheng-HH--Tewari-M--2012"><span class="Hyperlink">Pritchard et al., 2012</span></a>). miRNA mediate the gene expression either by target mRNA decay or translational repression. The former mostly seen in case of perfect complementarity as observed in plants while later mechanism in animals due to imperfect complementarity (<a href="#Ambros-V--2004"><span class="Hyperlink">Ambros, 2004</span></a>; <a href="#Ghosh-Z--Mallick-B--Chakrabarti-J--2009"><span class="Hyperlink">Ghosh et al., 2009</span></a>). miRNAs have several functions including regulation of cell physiology, proliferation, cell differentiation, apoptosis, hematopoiesis, limb morphogenesis, fat metabolism (<a href="#Srinivasan-S--Selvan-ST--Archunan-G--Gulyas-B--Padmanabhan-P--2013"><span class="Hyperlink">Srinivasan et al., 2013</span></a>), oncogenesis and viral infection. Several reports suggested aberrant expression profiles of miRNAs in various human diseases, thereby visualize the concept of miRNA-based therapeutics (<a href="#Stenvang-J--Petri-A--Lindow-M--Obad-S--Kauppinen-S--2012"><span class="Hyperlink">Stenvang et al., 2012</span></a>; <a href="#Mendell-JT--Olson-EN--2012"><span class="Hyperlink">Mendell and Olson, 2012</span></a>; <a href="#van-Rooij-E--Olson-EN--2012"><span class="Hyperlink">van Rooji and Olson, 2012</span></a>; <a href="#Thorsen-SB--Obad-S--Jensen-NF--Stenvang-J--Kauppinen-S--2012-."><span class="Hyperlink">Thorsen et al., 2012</span></a>; <a href="#van-Rooij-E--Olson-EN--2012"><span class="Hyperlink">van Rooji and Kauppinen, 2014</span></a>). <a href="#Lauring-AS--Jones-JO--Andino-R--2010"><span class="Hyperlink">Lauring et al. (2010)</span></a> proposed use of miRNA as one of the methodology for preparing live attenuated virus (LAV) vaccine, thus expanding the horizon of the miRNA work sphere. Controlled gene expression by miRNAs suppress tumor growth by regulating the factors of immune system put forward the concept of miRNA as vaccine candidate in case of cancer little further (<a href="#de-Rosa-F--Fanini-F-"><span class="Hyperlink">de Rosa et al., 2014</span></a>). Due to involvement in multiple biological processes miRNAs are the potential targets for designing new, modern therapeutic to combat cancer and viral diseases.</p>
		  <p class="Caps-on-First-Para ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction---- ParaOverride-1">MATURATION AND PROCESSING OF <span class="CharOverride-8">miRNAs</span></p>
		  <p class="Heading-1--Introduction---- ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">The linear canonical pathway (most common) of miRNA biogenesis comprises of two distinct phase i.e. the nuclear phase and the cytoplasmic phase. The generation of the primary miRNA (pri-miRNA) transcript of around 200 nucleotide to several thousand nucleotides length by RNA polymerase II enzyme (mostly) or by RNA polymerase III (rarely) (<a href="#Winter-J--Jung-S--Keller-S--Gregory-RI--Diederichs-S--2009"><span class="Hyperlink">Winter et al., 2009</span></a>) is the starting point in miRNA biogenesis (<a href="#Gottwein-E--Cullen-BR--2008"><span class="Hyperlink">Gottwein et al., 2008</span></a>; <a href="#Ghosh-Z--Mallick-B--Chakrabarti-J--2009"><span class="Hyperlink">Ghosh et al., 2009</span></a>; <a href="#Skalsky-RL--Cullen-BR--2010-"><span class="Hyperlink">Skalsky et al., 2010</span></a>). The nuclear RNase III enzyme Drosha along with accessory protein DGCR 8 further trim the pri-miRNA to generate precursor miRNA (Pre-miRNA) of 60 nucleotide length (<a href="#Zhuo-Y--Gao-G--et-al.--2013"><span class="Hyperlink">Zhuo et al., 2013</span></a>). The nuclear phase accomplished with the transportation of pre-miRNA into cytoplasm by the factor exportin-5 conjugated with RanGTP (<a href="#Kim-VN--2004-"><span class="Hyperlink">Kim, 2004</span></a>). GTP hydrolysis leads to the release of pre-miRNA into cytolplasm. At the onset of cytoplasmic phase the pre-miRNA is cleaved by Dicer (a cytoplasmic RNase III like enzyme) in association with its cofactor TRBP (Transactivating region RNA-binding protein (<a href="#Winter-J--Jung-S--Keller-S--Gregory-RI--Diederichs-S--2009"><span class="Hyperlink">Winter et al., 2009</span></a>). This in turn forms miRNA duplex intermediate (miRNA*/miRNA). Dicer loads one of the miRNA strand i.e. the guide strand (miRNA*) into RISCs (RNA induced silencing complexes), which is the miRNA effector complexes (<a href="#Gottwein-E--Cullen-BR--2008"><span class="Hyperlink">Gottwein et al., 2008</span></a>; <a href="#Ha-M--Kim-VN--2014-"><span class="Hyperlink">Ha et al., 2014</span></a>). The non-associated strand i.e. the passanger strand is subsequently degraded. RISC basically comprises of guide miRNA strand and one of the four Argonaute proteins. The miRNA in RISC then targets the complementary mRNA, which is either cleaved in case of perfect complementarity or undergone translational repression in case of imperfect complementarity. miRNA interaction can also leads to deadenylation or target decapping and results in rapid mRNA decay (<a href="#Wu-L--Fan-J--Belasco-JG--2006"><span class="Hyperlink">Wu et al., 2006</span></a>; <a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>). Translocation of the miRNA:mRNA complex to cytoplasmic foci is another method of translational repression (<a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction---- ParaOverride-1"><span class="CharOverride-8">miRNA</span> AND COMPETITIVE VIRAL AND HOST RNAs (cvhRNAs)</p>
		  <p class="Heading-1--Introduction---- ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">When a virus attacks a host cell, the viral transcript can act as a template for expressing its own proteins or can be a pathogen-associated molecular pattern (<a href="#Goubau-D--Deddouche-S--Reis"><span class="Hyperlink">Goubau et al., 2013</span></a>). In a virus infected cells there exist a complex network of interaction between the virus and host cell itself. The pool of common miRNAs means those miRNAs which can bind to both virus and host transcripts as well due to sequence complementarity, present at that moment affect the gene expression pattern of both virus and host. By observing these facts (<a href="#Li-C--Hu-J--et-al.--2014-"><span class="Hyperlink">Li et al., 2014</span>)</a> proposed the “competitive viral and host RNAs (cvhRNAs) hypothesis”. As per this hypothesis the viral miRNA able to snatch away the target sequence of host encoded miRNAs thus interfering the stability and translational efficiency of host mRNAs. Same is the case applicable for host miRNA to encounter viral pathogenesis. Thus the competitive environment interaction is the deciding factor for the viral infection to cherish or perish.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction---- ParaOverride-1">HOST-VIRUS INTERACTION FROM <span class="CharOverride-8">miRNA</span> WINDOW</p>
		  <p class="Heading-1--Introduction---- ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">There are several reports indicating the miRNA from virus which targets both viral mRNA and cellular mRNA to favour its existence in host environment. Similarly host produces its own miRNA that interacts with viral mRNA to favour itself, but reports also suggest the synergistic action of host miRNA with viral mRNA. So basically the interaction can be studied as follows.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Dual Actions of Viral <span class="CharOverride-8">miRNA</span></p>
			<p class="Body-Text ParaOverride-1">Viral miRNA can target both viral and host transcripts and favor its existence in the host. The clear motive of this interaction duo is successful establishment of the viral infection in the host. This can be fulfilled by actions like (i) latent and lytic life cycle balance for persistence of virus, (ii) immune evasion, (iii) prevention of apoptosis, (iv) viral replication regulation, (v) host cell cycle regulation and (vi) other measures (<a href="#Takane-K--Kanai-A--2011"><span class="Hyperlink">Takane et al., 2011</span></a>). It is not possible to enlist all suitable examples under each category. Some of the examples are discussed below.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-3">A. Viral<span class="CharOverride-10"> </span><span class="CharOverride-8">miRNA</span><span class="CharOverride-10"> </span>Aim For Viral Transcripts</p>
			<p class="Body-Text ParaOverride-1">Determination of the targets for viral miRNA on viral transcript is straight and quite easier due to simplicity of the viral genome. Viral miRNAs that are antisense to viral transcripts can regulate the viral infection in host by any of the above described five mechanisms, thus are potential targets for alleviating the virus infection in host.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text">For persistence infection virus must go for latent life cycle than lytic phase. Most of the herpes virus exhibit latent type of infection and miRNAs of virus also support this. For example miR-K12-9 of Kaposi’s sarcoma-associated herpesvirus (KSHV) suppresses expression of viral replication and transcription activator (RTA) factor thus maintain the latency (<a href="#Bellare-P--Ganem-D--2009-."><span class="Hyperlink">Bellare et al., 2009</span></a>). Similarly miR-15 of Infectious Laryngotracheitis Virus (ILTV) targets transcriptional activator ICP4 mRNA of ILTV gene and maintain the balance between latent and lytic phase of virus (<a href="#Waidner-LA--Burnside-J--Anderson-AS--et-al.--2011"><span class="Hyperlink">Waidner et al., 2011</span></a>). A suitable example of immune evasion action by viral miRNA is seen in SV-40 (Simian virus). Its miRNA i.e. miR-S1 expressed late in the infection but target viral T-antigen, thereby reducing its expression and ultimately results in insensitivity of infected cells to host cytotoxic T cells (<a href="#Sullivan-CS--Ganem-D--2005-"><span class="Hyperlink">Sullivan et al., 2005</span></a>). The Epstein Barr Virus (EBV) miR-BART represses viral LMP-1 protein that promotes host cell apoptosis. Thus prevent cell death and enhance virus survival (<a href="#Lo-AK--To-KF--Lo-KW--et-al.--2007"><span class="Hyperlink">Lo et al., 2007</span></a>). Role of viral miRNA regulating the viral replication through targeting immediate early viral protein can be visualized from Herpes Simplex Virus (HSV) infection (<a href="#Tang-S--Bertke-AS--Patel-A--Wang-K--Cohen-JI--Krause-PR--2008"><span class="Hyperlink">Tang et al., 2008</span></a>; <a href="#Umbach-JL--Nagel-MA--Cohrs-RJ--Gilden-DH--Cullen-BR--2009-"><span class="Hyperlink">Umbach et al., 2009</span></a>). miR-H2 of HSV-1 and HSV-2 targets ICP0 and down regulation of ICP0 protein expression (<a href="#Umbach-JL--Wang-K--Tang-S--Krause-PR--Mont-EK--et-al.--2010-."><span class="Hyperlink">Umbach et al., 2010</span></a>) leads to a strong latent stage of infection.HSV-1 miR-H6, which expressed during latency, suppress ICP4 and control viral replication and maintain latency (<a href="#Munson-DJ--Burch-AD--2012"><span class="Hyperlink">Munson and Burch, 2012</span></a>; <a href="#Mollaie-HR--Monavari-SH--Arabzadeh-SA--et-al.--2013-"><span class="Hyperlink">Mollaie et al., 2013</span></a>). ICP34.5 is situated antisense to miR-H3 and miR-H4. ICP34.5 is a virulence factor which inhibits PKR (Protein Kinase R) activity and attributes to neurovirulence. Represion of ICP34.5 by viral miRNAs may protect infected neurons being destroyed (<a href="#Tang-S--Bertke-AS--Patel-A--Wang-K--Cohen-JI--Krause-PR--2008"><span class="Hyperlink">Tang et al., 2008</span></a>; <a href="#Cullen-BR--2009"><span class="Hyperlink">Cullen, 2009</span></a>). Two miRNAs of ILTV lie anti-sense to ILTV ICP4 and down regulate ICP4 expression (<a href="#Waidner-LA--Burnside-J--Anderson-AS--et-al.--2011"><span class="Hyperlink">Waidner et al., 2011</span></a>) resulting in latency. </p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Heading-3">B. Viral <span class="CharOverride-8">miRNA</span> Aim For Viral Transcripts</p>
			<p class="Body-Text ParaOverride-1">A virus wants the cell it infected, to be alive for persistence infection. Thus keeping that as a goal, viral miRNAs target those cellular genes that involved in cell proliferation, survival, stress responses and antiviral defence pathways. In order to establish a successful latent infection, viral miRNA can promote viral replication either by prolonging cell survival or escaping the immune system surveillance. For example we can consider the KSHV miRNAs that target thrombospondin 1 (THBS1), a cellular component, whose main function is to inhibit the angiogenesis and cell growth by TGF<span class="CharOverride-11">β</span>, results in virus infected cells to perish in the system. Thus inhibition of THBS1 by viral miRNAs prevent cell death (<a href="#Samols-MA--Hu-J--Skalsky-RL--Renne-R--2005"><span class="Hyperlink">Samols et al., 2005</span></a>). Mostly the viral miRNAs target regulators of cell survival and growth, apoptotic factors so that the virus can maintain the latency. These facts are well supported by the work conducted by <a href="#Ziegelbauer-JM--Sullivan-CS--Ganem-D--2009"><span class="Hyperlink">Ziegelbauer et al. (2009)</span></a> on KSHV miR-K5, <a href="#Choy-EY--Siu-KL--Kok-KH--Lung-RW--Tsang-CM--et-al.--2008"><span class="Hyperlink">Choy et al. (2008)</span></a> on miR-BART5 and <a href="#Hansen-A--Henderson-S--Lagos-D--Nikitenko-L--Coulter-E--et-al.--2010"><span class="Hyperlink">Hansen et al. (2010)</span></a> on KSHV miR-K11 and miR-K 6. <a href="#Gottwein-E--Mukherjee-N--Sachse-C--Frenzel-C--M"><span class="Hyperlink">Gottwein et al. (2007)</span></a> reported the role of KSHV miR-K11 in regulating oxidative stress. KSHV miR-K12-3 targets host NFIB and help in latency of infection. Similarly HCMV (Human Cytomegalovirus) miR-UL 112-1, EBV miR-BART2, KSHV miR-K12-7 target host stress induced ligand MICB, thus bypassing the NK cell mediated killing of infected cells (<a href="#Nachmani-D--Stern-Ginossar-N--Sarid-R--Mandelboim-O--2009-."><span class="Hyperlink">Nachmani et al., 2009</span></a>; <a href="#Stern-Ginossar-N--Elefant-N--Zimmermann-A--Wolf-DG--Saleh-N--et-al.--2007"><span class="Hyperlink">Stern-Ginossar et al., 2007</span></a>). EBV miR-BART5 targets PUMA, a p53 regulated proapoptotic Bcl2 family member, thereby prevent the apoptosis of virus infected cells (<a href="#Choy-EY--Siu-KL--Kok-KH--Lung-RW--Tsang-CM--et-al.--2008"><span class="Hyperlink">Choy et al., 2008</span></a>). EBV miR-BHRF1 down regulate CXCL 11, thus surpassing T cell mediated immunity (<a href="#Xia-T--O-Hara-A--Araujo-I--Barreto-J--Carvalho-E--et-al.--2008"><span class="Hyperlink">Xia et al., 2008</span></a>). </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Dual action of cellular <span class="CharOverride-8">miRNAs</span></p>
			<p class="Body-Text">Assigning a separate work boundary for host encoded miRNAs and viral miRNA is difficult. In the competitive environment both have to work for their benefits. The function of cellular miRNA is not straight forward as it has both positive and negative impact on viral infection. Antiviral defense, suppression of viral replication is the fruitful outcome of cellular miRNA while supporting viral replication, inhibiting the host innate immunity is the dreaded outcome.</p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">As host encoded miRNAs have dual properties of being positive and negative action, it will be helpful to discuss under these heading rather based on its target. MicroRNA mediated antiviral defence can be seen in mammalian viruses such as primate foamy virus (PFV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Each case by itself enlights interesting aspect of microRNA-mediated host–virus interaction. Cellular microRNA mediating antiviral defence was seen in PFV (<a href="#Lecellier-CH--Dunoyer-P--Arar-K--Lehmann-Che-J--Eyquem-S--Himber-C--et-al.--2005"><span class="Hyperlink">Lecellier et al., 2005</span></a>). PFV replication is efficiently restricted by the cellular microRNA miR-32 targeting viral transcripts. Host miRNA mediated antiviral defense mechanism is seen in case of HCV replication (<a href="#Pedersen-IM--Cheng-G--Wieland-S--Volinia-S--Croce-CM--et-al.--2007-"><span class="Hyperlink">Pedersen et al., 2007</span></a>). Cellular miRNAs such as miR-24, miR-93 suppres Vesicular Stomatitis Virus (VSV) replication (<a href="#Otsuka-M--Jing-Q--Georgel-P--et-al.--2007"><span class="Hyperlink">Otsuka et al. 2007</span></a>). These cellular miRNAs target viral large protein and phosphoprotein genes and ultimately block viral replication. Indirect antiviral response by cellular miRNAs can be observed in case of HIV-1 replication (<a href="#Triboulet-R--Mari-B--Lin-YL--Chable-Bessia-C--Bennasser-Y--Lebrigand-K--et-al.--2007"><span class="Hyperlink">Triboulet et al., 2007</span></a>; <a href="#Vlachakis-D--Tsiliki-G--Pavlopoulou-A--et-al.--2013"><span class="Hyperlink">Vlachakis et al., 2013</span></a>). In the case of hepatitis C, a cell type-specific microRNA (miR-122) targeting the 5<span class="CharOverride-11">′</span> UTR of the viral transcript and modulate the viral levels. This explains how tissue or cell type-specific microRNAs can influence tropism of viruses (<a href="#Henke-JI--Goergen-D--Zheng-J--et-al.--2008"><span class="Hyperlink">Henke et al., 2008</span></a>; <a href="#Shwetha-S--Gouthamchandra-K--Chandra-M--et-al.--2013"><span class="Hyperlink">Shwetha et al., 2013</span></a>). The microRNAs targeting the viral transcripts were variable in individuals, suggesting that variation in expression levels may define the prognosis of infection. </p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">Cellular miRNAs are helpful in some aspects for viral infection. For example miR-155 of EBV affected B cell prevents apoptosis and inhibits host innate immunity (<a href="#Linnstaedt-SD--Gottwein-E--Skalsky-RL--Luftig-MA--Cullen-BR--2010"><span class="Hyperlink">Linnstaedt et al., 2010</span></a>). Cellular miRNA miR-132 regulate transcription factor thus have a control in viral replication as observed in HIV-1 (<a href="#Chiang-K--Liu-H--Rice-AP--2013-.-miR"><span class="Hyperlink">Chiang et al., 2013</span></a>), KSHV, HSV-1 and HCMV-1infections (<a href="#Lagos-D--Pollara-G--Henderson-S--et-al.--2008"><span class="Hyperlink">Lagos et al., 2010</span></a>). miR-122 stimulate HCV viral RNA stability and translation (<a href="#Roberts-AP--Lewis-AP--Jopling-CL--2011"><span class="Hyperlink">Roberts et al., 2011</span></a>). HIV-1 down regulates the expression of several host encoded miRNAs for its efficient replication and may also up regulates those miRNAs that are helpful for its survival (<a href="#Ghosh-Z--Mallick-B--Chakrabarti-J--2009"><span class="Hyperlink">Ghosh et al., 2009</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction---- ParaOverride-1">BIOINFORMATICS TOOLS TO EXPLORE <span class="CharOverride-8">miRNA</span> IN HOST-VIRUS INTERACTION</p>
		  <p class="Heading-1--Introduction---- ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">Being highly complex nature of the miRNA and target interaction, use of bioinformatics tools for prediction of miRNA target is a modern approach and less cumbersome and straightforward (<a href="#Ekimler-S--Sahin-K--2014"><span class="Hyperlink">Ekimler et al., 2014</span></a>). As compared to target prediction for miRNA in plant, which is quite straight and easier, the task in animal counterpart is more functionally diverse in nature (<a href="#Bartel-DP--2004"><span class="Hyperlink">Bartel, 2009</span></a>). So certain points are to be taken care of while going for miRNA target prediction. These are as follows:</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<ol>
			  <li class="Body-Text ParaOverride-2">The seed sequence i.e. about 2-7 nucleotides at the 5’ end of miRNA sequence follow the Watson-crick base pairing with 3’ UTR sequence of targeted transcripts. This is indeed essential to confer regulation of miRNA target (<a href="#Kim-VN--2004-"><span class="Hyperlink">Kim, 2004</span></a>). Along with this seed pairing, there is pairing at 3’ end of miRNA called as 3’-supplementary pairing which helps in improving specificity and affinity (<a href="#Bartel-DP--2004"><span class="Hyperlink">Bartel, 2009</span></a>; <a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>).</li>
				<li class="Body-Text ParaOverride-2">When there is weaker 5’ complementarity, additional compensatory base pairing is required at 3’ end of miRNA for regulation (<a href="#Brennecke-J--Stark-A--Russell-RB--Cohen-SM--2005"><span class="Hyperlink">Brenneck et al., 2005</span></a>). It does not necessarily mean that extensive pairing to the 3’ end of miRNA is only sufficient for regulation on its own without a minimal element of 5’ complementarity.</li>
				<li class="Body-Text ParaOverride-2">Identification of a conserved site for miRNA target increases the reliability of prediction programs (<a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>).</li>
				<li class="Body-Text ParaOverride-2">Target multiplicity means when one miRNA targets several genes suggesting combinatorial control of a single target by multiple miRNAs. This can be an important feature of miRNA targeting, very similar to the mode of transcription factor control of genes <span class="CharOverride-12">(</span><a href="#Doench-JG--Sharp-PA--2004"><span class="Hyperlink">Doench et al., 2004</span></a><span class="CharOverride-12">)</span> and multiple binding sites for a miRNA on the 3’ UTR can increase the efficiency of RNA silencing.</li>
				<li class="Body-Text ParaOverride-2">The strength of association between miRNA and its target depends upon the kinetics and thermodynamics properties of the bonding of both, which can be determined by RNA folding programs (<a href="#Wuchty-S--Fontana-W--Hofacker-IL--Schuster-P--1999"><span class="Hyperlink">Wuchty et al., 1999</span></a>).</li>
			</ol>
			<p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Heading-1--Introduction----"><span class="CharOverride-8">miRNA</span> TARGET PREDICTION TOOL</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">There are several bioinformatics tools available for the prediction of miRNA targets across species. It is not possible to enlist all. Few are described below.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">PicTar </p>
			<p class="Body-Text ParaOverride-1">It is an algorithm for prediction of microRNA targets. This website provides details regarding target prediction for miRNA in vertebrates, seven <span class="CharOverride-6">Drosophila</span> species and three nematode species. It also gives idea about the co-expressed human miRNA targets which are not conserved.<span class="CharOverride-4"> </span>PicTar is the first algorithm for analyzing miRNAs and its targets in co-expression with respect to specific time and place (<a href="#Krek-A--Grun-D--Poy-MN--Wolf-R-et-al.--2005"><span class="Hyperlink">Krek et al., 2005</span></a>). It computes a maximum likelihood score for a given transcript is targeted by several numbers of miRNAs. Based upon the most updated PicTar predictions, doRiNA database provides target predictions for human, mouse and worm (<a href="#Ekimler-S--Sahin-K--2014"><span class="Hyperlink">Ekimler et al., 2014</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">RNAhybrid</p>
			<p class="Body-Text ParaOverride-1">RNA-hybrid predicts multiple potential binding sites on target RNA for miRNAs and finds the energetically most favorable hybridization sites (<a href="#Rehmsmeier-M--Steffen-P--Hochsmann-M--Giegerich-R--2004"><span class="Hyperlink">Rehmsmeier et al., 2004</span></a>). Intramolecular hybridizations i.e. base pairings between target nucleotides or between miRNA nucleotides itself are not allowed. It allows many long targets to be searched in a short time. RNAhybrid, with its accompanying programs RNAcalibrate and RNAeffective, is available for download and as a Web tool on the Bielefeld Bioinformatics Server.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM- ParaOverride-1">The&#160;microRNA.org&#160;Resource (<a href="#Betel-D--Wilson-M--Gabow-A--Marks-DS--Sander-C--2008-."><span class="Hyperlink CharOverride-4">Betel et al., 2008</span></a>)</p>
			<p class="Body-Text ParaOverride-1">MicroRNA.org&#160;is an exclusive database of microRNA target predictions.&#160;Expression&#160;profiles and target predictions are based on miRanda algorithm. Here a user can explore (i) genes that are governed by a particular miRNA, (ii) for a single mRNA target several mi RNAs and (iii) miRNA expression profiles in several tissues.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Body-Text ParaOverride-1"><span class="CharOverride-13">miRanda-micro </span><span class="CharOverride-14">RNA Target Detection</span></p>
			<p class="Body-Text">This algorithm has been written in C languages. MiRanda was developed at the computational biology centre of Memorial sloan-kettering cancer centre. High complementarity between the miRNA and its target is the principle behind the prediction. The algorithm favours complementarity between 5’ end of miRNA and 3’ end of the transcripts and stability is evaluated by thermodynamically using the Vienna RNA folding packages (<a href="#Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"><span class="Hyperlink">Kumar et al., 2013</span></a>).</p>
		  <p class="Body-Text">&nbsp;</p>
			<p class="Heading-2--History-in-MM-"><span class="CharOverride-8">mir</span>DIP </p>
			<p class="Body-Text ParaOverride-1">mirDIP is the microRNA Data Integration Portal and as the name suggest it admixtures twelve miRNA prediction datasets obtained from six different miRNA prediction databases. Thus improves the accuracy and confidence of target prediction for miRNAs. One can use mirDIP in three different way of searching such as source search, characteristic search and tailored situation search (<a href="#Shirdel-EA--Xie-W--Mak-TW--Jurisica-I--2011"><span class="Hyperlink">Shridel et al., 2011</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-">Diana <span class="CharOverride-8">micro</span>T&#160;<span><img class="_idGenPageitem-1" src="AAVS_MH20150503150533_-Sahu-AR-et-al-web-resources/image/Image22598633_fmt.png" alt="0.00" /></span>&#160;(DIANA LAB)&#160;</p>
			<p class="Body-Text ParaOverride-1">Artifical neural network based prediction system is DIana microT 4.0 program. It looks for target genes for those miRNAs that are either user defined or annotated forms of these miRNAs. It calculates and uses the free energy of binding sites as an input data for prediction (<a href="#Ekimler-S--Sahin-K--2014"><span class="Hyperlink">Ekimler et al., 2014</span></a>).</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-2--History-in-MM-"><span class="CharOverride-8">mi</span>RT<span class="CharOverride-8">ar</span>&#160;</p>
			<p class="Body-Text ParaOverride-1">It is an integrated web portal for target identification of miRNAs exclusively for human. MicroRNA Target prediction (miRTar)&#160;is a tool that enables biologists to identify the biological functions and the regulatory relationship between miRNAs and their transcripts. It also provides perspective of information on the miRNA targets on&#160;alternatively spliced transcripts<span class="CharOverride-4">. </span>It supports four major features, such as:</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			
			  <li class="Body-Text ParaOverride-3">Identifying miRNA targets in humans.</li>
				<li class="Body-Text ParaOverride-3">miRNA prediction in all possible combinations.</li>
				<li class="Body-Text ParaOverride-3">View point on the regulation between miRNA and RNA alternate splicing.</li>
		  <li class="Body-Text ParaOverride-3">Linking of miRNA to metabolic pathway.</li>
			
			<p class="Heading-2--History-in-MM-">&nbsp;</p>
		  <p class="Heading-2--History-in-MM-">V<span class="CharOverride-8">i</span>T<span class="CharOverride-8">a</span></p>
			<p class="Body-Text ParaOverride-1">It is basically a database for host miRNA targets on virus genomes and viral transcripts (<a href="#Hsu-PW--Lin-LZ--Hsu-SD--Hsu-JB--Huang-HD--2007-."><span class="Hyperlink">Hsu et al., 2007</span></a>). The database has a collection of known host miRNAs, viral miRNAs and host miRNA targets on viruses. So it will be helpful in investigating host virus interaction through host miRNA window. It acquires virus miRNA data from other databases like miRBase, ICTV, VirGen, VBRC and predict the targets for cellular miRNAs by using miRanda and TargetScan. This is also give idea about human miRNA expression in virus infected tissues. It also helps users to investigate the microRNA roles in viral existence. ViTa was developed by Bidlab in 2005.&#9;</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">CONCLUSION</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">In case of post transcriptional gene regulation miRNA is an important key factor. The role of miRNA in host- virus interaction cannot be neglected as this interaction opens several pathways to study molecular basis of pathogenesis of virus infection. The relevant study regarding this interaction enlightens the present understanding on possible interaction between host and virus and enriches our knowledge to develop new age vaccine based on miRNA or to develop novel therapeutic strategy to combat virus infection. The manipulation of miRNA in host virus interaction may possible help us to ameliorate the virus infection effectively in near future.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">CONFLICT OF INTEREST</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">The authors have no conflict of Interest.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">AUTHORS’ CONTRIBUTIONS</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">Aditya Prasad Sahoo, Ashok Kumar Tiwari and Ravi Kumar Gandham gave the concept of the manuscript and overviewed bioinformatics portion. Amit Ranjan Sahu and Arpita Padhy drafted and revised the whole manuscript. Sajad Ahmad Wani, Amod Kumar and Govindarajan Bhuvana Priya equally contributed matter to the manuscript. All the authors have read and approved the manuscript.</p>
			<p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Heading-1--Introduction----">ACKNOWLEDGEMENTS</p>
		  <p class="Heading-1--Introduction----">&nbsp;</p>
			<p class="Body-Text ParaOverride-1">The authors acknowledge the financial support provided by Department of Biotechnology (DBT), Government of India.</p>
		  <p class="Body-Text ParaOverride-1">&nbsp;</p>
			<p class="Heading-1--Introduction----">REFERENCES</p>
		
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Ambros-V--2004"></a>Ambros V (2004). The functions of animal microRNAs. Nature. 431(7006): 350-355. <a href="http://dx.doi.org/10.1038/nature0287"><span class="Hyperlink">http://dx.doi.org/10.1038/nature0287</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Bartel-DP--2004"></a>Bartel DP (2004). MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell. 116(2): 281-297. <a href="http://dx.doi.org/10.1016/S0092-8674(04)00045-5"><span class="Hyperlink">http://dx.doi.org/10.1016/S0092-8674(04)00045-5</span></a> </li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Bartel-DP--2009"></a>Bartel DP (2009). MicroRNAs: Target Recognition and Regulatory Functions. Cell. 136(2): 215-233. <a href="http://dx.doi.org/10.1016/j.cell.2009.01.002 "><span class="Hyperlink">http://dx.doi.org/10.1016/j.cell.2009.01.002</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Bellare-P--Ganem-D--2009-."></a>Bellare P, Ganem D (2009). Regulation of KSHV lytic switch protein expression by a virus-encoded microRNA: an evolutionary adaptation that fine-tunes lytic reactivation. Cell Host Microbe. 6(6): 570–575. <a href="http://dx.doi.org/10.1016/j.chom.2009.11.008"><span class="Hyperlink">http://dx.doi.org/10.1016/j.chom.2009.11.008</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Betel-D--Wilson-M--Gabow-A--Marks-DS--Sander-C--2008-."></a>Betel D, Wilson M, Gabow A, Marks DS, Sander C (2008). The microRNA.org resource: targets and expression. Nucleic Acids Res. 36(Database Issue): D149–D153.</li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Brennecke-J--Stark-A--Russell-RB--Cohen-SM--2005"></a>Brennecke J, Stark A, Russell RB, Cohen SM (2005). Principles of microRNA-target recognition. PLoS Biol. 3(3): e85. <a href="http://dx.doi.org/10.1371/journal.pbio.0030085"><span class="Hyperlink">http://dx.doi.org/10.1371/journal.pbio.0030085</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Chiang-K--Liu-H--Rice-AP--2013-.-miR"></a>Chiang K, Liu H, Rice AP (2013). miR-132 enhances HIV-1 replication. Virology. 438(1): 1-4. <a href="http://dx.doi.org/10.1016/j.virol.2012.12.016"><span class="Hyperlink">http://dx.doi.org/10.1016/j.virol.2012.12.016</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Choy-EY--Siu-KL--Kok-KH--Lung-RW--Tsang-CM--et-al.--2008"></a>Choy EY, Siu KL, Kok KH, Lung RW, Tsang CM, To KF, Kwong DL, Tsao SW, Jin DY (2008). An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival. J. Exp. Med. 205(11): 2551–2560. <a href="http://dx.doi.org/10.1084/jem.20072581"><span class="Hyperlink">http://dx.doi.org/10.1084/jem.20072581</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Cullen-BR--2009"></a>Cullen BR (2009). Viral and cellular messenger RNA targets of viral microRNAs. Nature. 457(7228): 421–425. <a href="http://dx.doi.org/10.1038/nature07757"><span class="Hyperlink">http://dx.doi.org/10.1038/nature07757</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="de-Rosa-F--Fanini-F-"></a>de Rosa F, Fanini F, Guidoboni M, Vannini I, Amadori D, Ridolfi R, Ridolfi L, Fabbri M (2014). MicroRNAs and dendritic cell-based vaccination in melanoma patients. Melanoma Res. 24(3): 181-189. <a href="http://dx.doi.org/10.1097/CMR.0000000000000058"><span class="Hyperlink">http://dx.doi.org/10.1097/CMR.0000000000000058</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Doench-JG--Sharp-PA--2004"></a>Doench JG, Sharp PA (2004). Specificity of microRNA target selection in translational repression. Gen. Dev. 18(5): 504–511. <a href="http://dx.doi.org/10.1101/gad.1184404"><span class="Hyperlink">http://dx.doi.org/10.1101/gad.1184404</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Ekimler-S--Sahin-K--2014"></a>Ekimler S, Sahin K (2014). Computational methods for microRNA target prediction. Genes. 5(3): 671-683. <a href="http://dx.doi.org/10.3390/genes5030671"><span class="Hyperlink">http://dx.doi.org/10.3390/genes5030671</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Ghosh-Z--Mallick-B--Chakrabarti-J--2009"></a>Ghosh Z, Mallick B, Chakrabarti J (2009). Cellular versus viral microRNAs in host–virus interaction. Nucleic Acids Res. 37(4): 1035–1048. <a href="http://dx.doi.org/10.1093/nar/gkn1004"><span class="Hyperlink">http://dx.doi.org/10.1093/nar/gkn1004</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Gottwein-E--Cullen-BR--2008"></a>Gottwein E, Cullen BR (2008). Viral and Cellular MicroRNAs as Determinants of Viral Pathogenesis and Immunity. Cell Host Microbe. 3(6): 375-387. <a href="http://dx.doi.org/10.1016/j.chom.2008.05.002"><span class="Hyperlink">http://dx.doi.org/10.1016/j.chom.2008.05.002</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Gottwein-E--Mukherjee-N--Sachse-C--Frenzel-C--M"></a>Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, Chi JT, Braich R, Manoharan M, Soutschek J, Ohler U, Cullen BR (2007). A viral microRNA functions as an orthologue of cellular miR-155. Nature. 450(7172): 1096–1099. <a href="http://dx.doi.org/10.1038/nature05992"><span class="Hyperlink">http://dx.doi.org/10.1038/nature05992</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Goubau-D--Deddouche-S--Reis"></a>Goubau D, Deddouche S, Reis E, Sousa C (2013). Cytosolic sensing of viruses. Immunity. 38(5): 855–869. <a href="http://dx.doi.org/10.1016/j.immuni.2013.05.007"><span class="Hyperlink">http://dx.doi.org/10.1016/j.immuni.2013.05.007</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Griffiths-Jones-S--Saini-HK--Dongen-SV--Enright-AJ--2008"></a>Griffiths-Jones S, Saini HK, Dongen SV, Enright AJ (2008). miRBase: tools for microRNA genomics. Nucleic Acids Res. 36(Database issue): D154–D158.</li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Ha-M--Kim-VN--2014-"></a>Ha M, Kim VN (2014). Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 15(8): 509-524. <a href="http://dx.doi.org/10.1038/nrm3838"><span class="Hyperlink">http://dx.doi.org/10.1038/nrm3838</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Hansen-A--Henderson-S--Lagos-D--Nikitenko-L--Coulter-E--et-al.--2010"></a>Hansen A, Henderson S, Lagos D, Nikitenko L, Coulter E, Roberts S, Gratrix F, Plaisance K, Renne R, Bower M, Kellam P, Boshoff C (2010). KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming. Gen. Develop. 24(2): 195–205. <a href="http://dx.doi.org/10.1101/gad.553410"><span class="Hyperlink">http://dx.doi.org/10.1101/gad.553410</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Henke-JI--Goergen-D--Zheng-J--et-al.--2008"></a>Henke JI, Goergen D, Zheng J, Song Y, Schüttler CG, Fehr C, Jünemann C, Niepmann M (2008). microRNA-122 stimulates translation of hepatitis C virus RNA. EMBO J. 27(24): 3300-3310. <a href="http://dx.doi.org/10.1038/emboj.2008.244"><span class="Hyperlink">http://dx.doi.org/10.1038/emboj.2008.244</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Hsu-PW--Lin-LZ--Hsu-SD--Hsu-JB--Huang-HD--2007-."></a>Hsu PW, Lin LZ, Hsu SD, Hsu JB, Huang HD (2007). ViTa: prediction of host microRNAs targets on viruses. Nucleic Acids Res. 35(Database issue): D381–D385. <a href="http://dx.doi.org/10.1093/nar/gkl1009"><span class="Hyperlink">http://dx.doi.org/10.1093/nar/gkl1009</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Kim-VN--2004-"></a>Kim VN (2004). MicroRNA precursors in motion: exportin-5 mediates their nuclear export. Trends Cell Biol. 14(4): 156–159. <a href="http://dx.doi.org/10.1016/j.tcb.2004.02.006"><span class="Hyperlink">http://dx.doi.org/10.1016/j.tcb.2004.02.006</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Kozomara-A--Griffiths-Jones-S--2014-"></a>Kozomara A, Griffiths-Jones S (2014). miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 42(Database issue): D68-D73. <a href="http://dx.doi.org/10.1093/nar/gkt1181"><span class="Hyperlink">http://dx.doi.org/10.1093/nar/gkt1181</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Krek-A--Grun-D--Poy-MN--Wolf-R-et-al.--2005"></a>Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, MacMenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005). Combinatorial microRNA target predictions. Nat. Genet. 37(5): 495-500. <a href="http://dx.doi.org/10.1038/ng1536"><span class="Hyperlink">http://dx.doi.org/10.1038/ng1536</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Kumar-A--Muhasin-Asaf-VN--Srivastava-K--Abdul-Rahim--Chaudhary-JK--Panigrahi-M--2013"></a>Kumar A, Muhasin Asaf VN, Srivastava K, Abdul Rahim, Chaudhary JK, Panigrahi M (2013). MicroRNA: biogenesis and computational target identification: a review. Vet. World. 6(10): 761-765. <a href="http://dx.doi.org/10.14202/vetworld.2013.761-765"><span class="Hyperlink">http://dx.doi.org/10.14202/vetworld.2013.761-765</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Lagos-D--Pollara-G--Henderson-S--et-al.--2008"></a>Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS, Gotch F, Boshoff C (2008). miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator. Nat. Cell Biol. 12(5): 513-519. <a href="http://dx.doi.org/10.1038/ncb2054"><span class="Hyperlink">http://dx.doi.org/10.1038/ncb2054</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Lauring-AS--Jones-JO--Andino-R--2010"></a>Lauring AS, Jones JO, Andino R (2010). Rationalizing the development of live attenuated virus vaccines. Nat. Biotechnol. 28(6): 573-579. <a href="http://dx.doi.org/10.1038/nbt.1635"><span class="Hyperlink">http://dx.doi.org/10.1038/nbt.1635</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Lecellier-CH--Dunoyer-P--Arar-K--Lehmann-Che-J--Eyquem-S--Himber-C--et-al.--2005"></a>Lecellier CH, Dunoyer P, Arar K, Lehmann-Che J, Eyquem S, Himber C, Saïb A, Voinnet O (2005). A cellular microRNA mediates antiviral defense in human cells. Science. 308(5721): 557–560. <a href="http://dx.doi.org/10.1126/science.1108784"><span class="Hyperlink">http://dx.doi.org/10.1126/science.1108784</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Li-C--Hu-J--et-al.--2014-"></a>Li C, Hu J, Hao J, Zhao B, Wu B, Sun L, Peng S, Gao GF, Meng S (2014). Competitive virus and host RNAs: the interplay of a hidden virus and host interaction. Protein Cell. 5(5): 348–356. <a href="http://dx.doi.org/10.1007/s13238-014-0039-y"><span class="Hyperlink">http://dx.doi.org/10.1007/s13238-014-0039-y</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Linnstaedt-SD--Gottwein-E--Skalsky-RL--Luftig-MA--Cullen-BR--2010"></a>Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA, Cullen BR (2010). Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J. Virol. 84(22): 11670-11678. <a href="http://dx.doi.org/10.1128/JVI.01248-10"><span class="Hyperlink">http://dx.doi.org/10.1128/JVI.01248-10</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Lo-AK--To-KF--Lo-KW--et-al.--2007"></a>Lo AK, To KF, Lo KW, Lung RW, Hui JW, Liao G, Hayward SD (2007). Modulation of LMP1 protein expression by EBV-encoded microRNAs. Proc. Nat. Acad. Sci. USA, 104(41): 16164–16169. <a href="http://dx.doi.org/10.1073/pnas.0702896104"><span class="Hyperlink">http://dx.doi.org/10.1073/pnas.0702896104</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><span class="Hyperlink"><a id="Mendell-JT--Olson-EN--2012"></a></span>Mendell JT, Olson EN (2012). MicroRNAs in stress signaling and human disease. Cell 148(6): 1172 – 1187. <a href="http://dx.doi.org/10.1016/j.cell.2012.02.005"><span class="Hyperlink">http://dx.doi.org/10.1016/j.cell.2012.02.005</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Mollaie-HR--Monavari-SH--Arabzadeh-SA--et-al.--2013-"></a>Mollaie HR, Monavari SH, Arabzadeh SA, Shamsi-Shahrabadi M, Fazlalipour M, Afshar RM (2013). RNAi and miRNA in viral infections and cancers. Asian Pac. J. Cancer Prev. 14(12): 7045-7056. <a href="http://dx.doi.org/10.7314/APJCP.2013.14.12.7045"><span class="Hyperlink">http://dx.doi.org/10.7314/APJCP.2013.14.12.7045</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Munson-DJ--Burch-AD--2012"></a>Munson DJ, Burch AD (2012). A novel miRNA produced during lytic HSV-1 infection is important for efficient replication in tissue culture. Arch. Virol. 157(9): 1677-1688.<a href="http://dx.doi.org/10.1007/s00705-012-1345-4"><span class="Hyperlink">http://dx.doi.org/10.1007/s00705-012-1345-4</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Nachmani-D--Stern-Ginossar-N--Sarid-R--Mandelboim-O--2009-."></a>Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O (2009). Diverse herpesvirus microRNAs target the stress-induced immune ligand MICB to escape recognition by natural killer cells. Cell Host Microbe. 5(4): 376–385. <a href="http://dx.doi.org/10.1016/j.chom.2009.03.003"><span class="Hyperlink">http://dx.doi.org/10.1016/j.chom.2009.03.003</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Otsuka-M--Jing-Q--Georgel-P--et-al.--2007"></a>Otsuka M, Jing Q, Georgel P, New L, Chen J, Mols J, Kang YJ, Jiang Z, Du X, Cook R, Das SC, Pattnaik AK, Beutler B, Han J (2007). Hypersusceptibility to vescicular stomatis virus infection in Dicer1-deficient mice is due to impaired miR24 and miR93 expression. Immunity. 27(1): 123-134. <a href="http://dx.doi.org/10.1016/j.immuni.2007.05.014"><span class="Hyperlink">http://dx.doi.org/10.1016/j.immuni.2007.05.014</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Pedersen-IM--Cheng-G--Wieland-S--Volinia-S--Croce-CM--et-al.--2007-"></a>Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007). Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature. 449(7164): 919-922. <a href="http://dx.doi.org/10.1038/nature06205"><span class="Hyperlink">http://dx.doi.org/10.1038/nature06205</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Pritchard-CC--Cheng-HH--Tewari-M--2012"></a>Pritchard CC, Cheng HH, Tewari M (2012). MicroRNA profiling: approaches and considerations. Nat. Rev. Genet. 13(5): 358-369. <a href="http://dx.doi.org/10.1038/nrg3198"><span class="Hyperlink">http://dx.doi.org/10.1038/nrg3198</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Rehmsmeier-M--Steffen-P--Hochsmann-M--Giegerich-R--2004"></a>Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R (2004). Fast and effective prediction of microRNA/target duplexes. RNA. 10(10): 1507-1517. <a href="http://dx.doi.org/10.1261/rna.5248604"><span class="Hyperlink">http://dx.doi.org/10.1261/rna.5248604</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Roberts-AP--Lewis-AP--Jopling-CL--2011"></a>Roberts AP, Lewis AP, Jopling CL (2011). miR-122 activates hepatitis C virus translation by a specialized mechanism requiring particular RNA components. Nucleic Acids Res. 39(17): 7716-7729. <a href="http://dx.doi.org/10.1093/nar/gkr426"><span class="Hyperlink">http://dx.doi.org/10.1093/nar/gkr426</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Samols-MA--Hu-J--Skalsky-RL--Renne-R--2005"></a>Samols MA, Hu J, Skalsky RL, Renne R (2005). Cloning and identification of a microRNA cluster within the latency-associated region of Kaposi’s sarcoma-associated herpesvirus. J. Virol. 79(14): 9301–9305. <a href="http://dx.doi.org/10.1128/JVI.79.14.9301-9305.2005"><span class="Hyperlink">http://dx.doi.org/10.1128/JVI.79.14.9301-9305.2005</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Scaria-V--Hariharan-M--et-al.--2007"></a>Scaria V, Hariharan M, Pillai B, Maiti S, Brahmachari SK (2007). Host–virus genome interactions: macro roles for microRNAs. Cell. Microbiol. 9(12): 2784–2794. <a href="http://dx.doi.org/10.1111/j.1462-5822.2007.01050.x"><span class="Hyperlink">http://dx.doi.org/10.1111/j.1462-5822.2007.01050.x</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Shirdel-EA--Xie-W--Mak-TW--Jurisica-I--2011"></a>Shirdel EA, Xie W, Mak TW, Jurisica I (2011). NAViGaTing the Micronome-Using Multiple MicroRNA Prediction Databases to Identify Signalling Pathway-Associated MicroRNAs. PLoS ONE. 6(2): e17429. <a href="http://dx.doi.org/10.1371/journal.pone.0017429"><span class="Hyperlink">http://dx.doi.org/10.1371/journal.pone.0017429</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Shwetha-S--Gouthamchandra-K--Chandra-M--et-al.--2013"></a>Shwetha S, Gouthamchandra K, Chandra M, Ravishankar B, Khaja MN, Das S (2013). Circulating miRNA profile in HCV infected serum: novel insight into pathogenesis. Sci. Reprod. 3: 1555. <a href="http://dx.doi.org/10.1038/srep01555"><span class="Hyperlink">http://dx.doi.org/10.1038/srep01555</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Skalsky-RL--Cullen-BR--2010-"></a>Skalsky RL, Cullen BR (2010). Viruses, microRNAs and host interaction. Ann. Rev. Microbiol. 64: 123–141. <a href="http://dx.doi.org/10.1146/annurev.micro.112408.134243"><span class="Hyperlink">http://dx.doi.org/10.1146/annurev.micro.112408.134243</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Srinivasan-S--Selvan-ST--Archunan-G--Gulyas-B--Padmanabhan-P--2013"></a>Srinivasan S, Selvan ST, Archunan G, Gulyas B, Padmanabhan P (2013). MicroRNAs-the next generation therapeutic targets in human diseases. Theranostics. 3(12): 930-942. <a href="http://dx.doi.org/10.7150/thno.7026"><span class="Hyperlink">http://dx.doi.org/10.7150/thno.7026</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Stenvang-J--Petri-A--Lindow-M--Obad-S--Kauppinen-S--2012"></a>Stenvang J, Petri A, Lindow M, Obad S, Kauppinen S (2012). Inhibition of microRNA function by antimiR oligonucleotides. Silence. 3(1): 1. <a href="http://dx.doi.org/10.1186/1758-907X-3-1"><span class="Hyperlink">http://dx.doi.org/10.1186/1758-907X-3-1</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Stern-Ginossar-N--Elefant-N--Zimmermann-A--Wolf-DG--Saleh-N--et-al.--2007"></a>Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, Horwitz E, Prokocimer Z, Prichard M, Hahn G, Goldman-Wohl D, Greenfield C, Yagel S, Hengel H, Altuvia Y, Margalit H, Mandelboim O (2007). Host immune system gene targeting by a viral miRNA. Science. 317(5836): 376–381. <a href="http://dx.doi.org/10.1126/science.1140956">http://dx.doi.org/10.1126/science.1140956</a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Sullivan-CS--Ganem-D--2005-"></a>Sullivan CS, Ganem D (2005). MicroRNAs and Viral infection. Mol. Cell. 20(1): 3–7. <a href="http://dx.doi.org/10.1016/j.molcel.2005.09.012"><span class="Hyperlink">http://dx.doi.org/10.1016/j.molcel.2005.09.012</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Takane-K--Kanai-A--2011"></a>Takane K, Kanai A (2011). Vertebrate virus encoded microRNAs and their sequence conservation. Jpn. J. Infect. Dis. 64(5): 357-366.</li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Tang-S--Bertke-AS--Patel-A--Wang-K--Cohen-JI--Krause-PR--2008"></a>Tang S, Bertke AS, Patel A, Wang K, Cohen JI, Krause PR (2008). 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(31): 10931–10936. <a href="http://dx.doi.org/10.1073/pnas.0801845105"><span class="Hyperlink">http://dx.doi.org/10.1073/pnas.0801845105</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Thorsen-SB--Obad-S--Jensen-NF--Stenvang-J--Kauppinen-S--2012-."></a>Thorsen SB, Obad S, Jensen NF, Stenvang J, Kauppinen S (2012). The therapeutic potential of microRNAs in cancer. Cancer J. 18(3): 275 – 284. <a href="http://dx.doi.org/10.1097/PPO.0b013e318258b5d"><span class="Hyperlink">http://dx.doi.org/10.1097/PPO.0b013e318258b5d</span></a>6</li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Thum-T--2012"></a>Thum T (2012). MicroRNA therapeutics in cardiovascular medicine. EMBO Mol. Med. 4(1): 3 – 14. <a href="http://dx.doi.org/10.1002/emmm.201100191"><span class="Hyperlink">http://dx.doi.org/10.1002/emmm.201100191</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Triboulet-R--Mari-B--Lin-YL--Chable-Bessia-C--Bennasser-Y--Lebrigand-K--et-al.--2007"></a>Triboulet R, Mari B, Lin YL, Chable-Bessia C, Bennasser Y, Lebrigand K, Cardinaud B, Maurin T, Barbry P, Baillat V, Reynes J, Corbeau P, Jeang KT, Benkirane M (2007). Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science. 315(5818): 1579–1582. <a href="http://dx.doi.org/10.1126/science.1136319"><span class="Hyperlink">http://dx.doi.org/10.1126/science.1136319</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Umbach-JL--Nagel-MA--Cohrs-RJ--Gilden-DH--Cullen-BR--2009-"></a>Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR (2009). Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. J. Virol. 83(20): 10677–10683. <a href="http://dx.doi.org/10.1128/JVI.01185-09"><span class="Hyperlink">http://dx.doi.org/10.1128/JVI.01185-09</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Umbach-JL--Wang-K--Tang-S--Krause-PR--Mont-EK--et-al.--2010-."></a>Umbach JL, Wang K, Tang S, Krause PR, Mont EK, Cohen JI, Cullen BR (2010). Identification of viral microRNAs expressed in human sacral ganglia latently infected with herpes simplex virus 2. J. Virol. 84(2): 1189–1192. <a href="http://dx.doi.org/10.1128/JVI.01712-09 "><span class="Hyperlink">http://dx.doi.org/10.1128/JVI.01712-09</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="van-Rooij-E--Olson-EN--2012"></a>van Rooij E, Olson EN (2012). MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles. Nat. Rev. Drug Discov. 11(11): 860 – 872. <a href="http://dx.doi.org/10.1038/nrd3864"><span class="Hyperlink">http://dx.doi.org/10.1038/nrd3864</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US">v<a id="an-Rooji-E--Kauppinen-S--2014-"></a>an Rooji E, Kauppinen S (2014). Development of microRNA therapeutics is coming of age. EMBO Mol. Med. 6(7): 851-864. <a href="http://dx.doi.org/10.15252/emmm.201100899"><span class="Hyperlink">http://dx.doi.org/10.15252/emmm.201100899</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Vlachakis-D--Tsiliki-G--Pavlopoulou-A--et-al.--2013"></a>Vlachakis D, Tsiliki G, Pavlopoulou A, Roubelakis MG, Tsaniras SC, Kossida S (2013). Antiviral stratagems against HIV-1 using RNA Interference (RNAi) technology. Evol. Bioinfo. Online. 9: 203-213.</li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Waidner-LA--Burnside-J--Anderson-AS--et-al.--2011"></a>Waidner LA, Burnside J, Anderson AS,<span class="CharOverride-16"> </span>Bernberg EL, German MA, Meyers BC, Green PJ, Morgan RW (2011). A microRNA of infectious laryngotracheitis virus can downregulate and direct cleavage of ICP4 mRNA. Virology. 411(1): 25–31. <a href="http://dx.doi.org/10.1016/j.virol.2010.12.023"><span class="Hyperlink">http://dx.doi.org/10.1016/j.virol.2010.12.023</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Wiggins-JF--Ruffino-L--Kelnar-K--Omotola-M--Patrawala-L--et-al.--2010"></a>Wiggins JF, Ruffino L, Kelnar K, Omotola M, Patrawala L, Brown D, Bader AG (2010). Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 70(14): 5923 – 5930. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-10-0655"><span class="Hyperlink">http://dx.doi.org/10.1158/0008-5472.CAN-10-0655</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Winter-J--Jung-S--Keller-S--Gregory-RI--Diederichs-S--2009"></a>Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat. Cell Biol. 11(3): 228-234. <a href="http://dx.doi.org/10.1038/ncb0309-228"><span class="Hyperlink">http://dx.doi.org/10.1038/ncb0309-228</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Wu-L--Fan-J--Belasco-JG--2006"></a>Wu L, Fan J, Belasco JG (2006). MicroRNA direct rapid deadenylation of mRNA. Proc. Natl. Acad. Sci. USA. 103(11): 4034-4039. <a href="http://dx.doi.org/10.1073/pnas.0510928103"><span class="Hyperlink">http://dx.doi.org/10.1073/pnas.0510928103</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Wuchty-S--Fontana-W--Hofacker-IL--Schuster-P--1999"></a>Wuchty S, Fontana W, Hofacker IL, Schuster P (1999). Complete suboptimal folding of RNA and the stability of secondary structures. Biopolymers. 49(2): 145–165. <a href="http://dx.doi.org/10.1002/(SICI)1097-0282(199902)49:2&lt;145::AID-BIP4&gt;3.3.CO;2-7"><span class="Hyperlink">http://dx.doi.org/10.1002/(SICI)1097-0282(199902)49:2&lt;145::AID-BIP4&gt;3.3.CO;2-7</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Xia-T--O-Hara-A--Araujo-I--Barreto-J--Carvalho-E--et-al.--2008"></a>Xia T, O’Hara A, Araujo I, Barreto J, Carvalho E,  Sapucaia JB, Ramos JC, Luz E, Pedroso C, Manrique M, Toomey NL, Brites C, Dittmer DP, Harrington WJ Jr (2008). EBV microRNAs in primary lymphomas and targeting of CXCL-11 by ebv-mir-BHRF1-3. Cancer Res. 68(5): 1436–1442. <a href="http://dx.doi.org/10.1158/0008-5472.CAN-07-5126 "><span class="Hyperlink">http://dx.doi.org/10.1158/0008-5472.CAN-07-5126</span></a></li>
				<li class="References ParaOverride-5" xml:lang="en-US"><a id="Zhuo-Y--Gao-G--et-al.--2013"></a>Zhuo Y, Gao G, Shi JA, Zhou X, Wang X (2013). miRNAs: Biogenesis, origin and evolution, function on virus-host interaction. Cell Physiol. Biochem. 32(3): 499-510. <a href="http://dx.doi.org/10.1159/000354455"><span class="Hyperlink">http://dx.doi.org/10.1159/000354455</span></a></li>
		  <li class="References ParaOverride-5" xml:lang="en-US"><a id="Ziegelbauer-JM--Sullivan-CS--Ganem-D--2009"></a>Ziegelbauer JM, Sullivan CS, Ganem D (2009). Tandem array-based expression screens identify host mRNA targets of virus-encoded microRNAs. Nat. Genet. 41(1): 130–134. <a href="http://dx.doi.org/10.1038/ng.266"><span class="Hyperlink">http://dx.doi.org/10.1038/ng.266</span></a></li>
			
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