Although the vast majority of bacteria are innocuous or even beneficial to mammalian hosts, bacterial pathogens are the causative agents of several relevant diseases worldwide, such as foodborne illnesses caused by listeria monocytogenes and salmonella species, peptic ulcers and gastric cancers associated with helicobacter pylori and tuberculosis caused by mycobacterium tuberculosis. It is known that the expression profiles of host mirnas can be reshaped by viruses. Ramkat1,2, margit laimer1 1plant biotechnology unit pbu, department biotechnology, university of natural resources and life sciences, bokuvibt, vienna, austria, 2department of biological. While mirnas of viral and cellular origin have been demonstrated to modulate viral gene expression and host immune responses. Intended use the mirzip virus library is a tool that enables the study of phenotypic effects associated with the knockdown of individual. Although host mirnas may target the hiv1 rna genome, they have host genes as their normal biological targets. Viruses, micrornas, and host interactions oregon health. Oncolytic viruses kill cancer cells, sparing healthy tissues, and provoke. The role of rnai and micrornas in animal virus replication and antiviral immunity jennifer l. Micrornas mirnas are a new class of 1823 nucleotide long noncoding rnas that play critical roles in a wide spectrum of biological processes. Developing a virusmicrorna interactome using cytoscape. Survey and summary cellular versus viral micrornas in hostvirus interaction zhumur ghosh1, bibekanand mallick1 and jayprokas chakrabarti1,2 1computational biology group, indian association for the cultivation of science, jadavpur, calcutta 700 032. Cullen1 department of molecular genetics and microbiology and center for virology, duke university medical center, durham, north carolina 27710, usa the closely related microrna mirna and rnai path.
In vivo identification of interactions between active. Therefore four different classes of mirnatarget interaction can impact the outcome of an infection. Hepatitis c virus hcv infection changes the expression of host mirnas in vitro and in vivo, while host micrornas mirnas in turn regulate hcv life cycle through directly binding to hcv rna andor indirectly targeting cellular mrnas. Jun 12, 2012 the most common etiologic agents causing chronic hepatitis are hepatitis c and b viruses hcv and hbv, respectively. Host pathogen interactions result in signaling and physiological modi. These molecules regulate gene expression at the posttranscriptional level and are differentially expressed in viral acute respiratory infections aris, which are responsible for high morbidity and mortality around the world. Despite the availability of an effective prophylactic vaccine for nearly three decades, hbv remains the cause of a number of important public health problems. Request pdf the roles of micrornas and pirnas in virushost interactions. Micrornas mirnas, a class of small noncoding regulatory rnas, have been detected in a variety of organisms ranging from ancient unicellular eukaryotes to mammals.
Micrornas mirnas are singlestranded rnas of 1724 nt. The sizes of the predicted arabidopsis hairpins are more variable than those of animals. This sets up a complex web of potential regulatory interactions. Micrornas mirnas are a new class of small noncoding rnas that regulate gene expression posttranscriptionally. Of particular relevance to hostpathogen interactions, mirnas play a role in regulating the innate immune response, adaptive immune cell. Although some of thearabidopsis precursor predictions resemble those of c. Because dna viruses generally employ host pol ii machinery to express their genes, it is expected that many such viruses will encode mirnasa prediction that was validated by pfeffer et al. This interplay has important consequences, both for the virus and the host. These mirnas are involved in the modulation of both innate and adaptive immune. There are potential problems in targeting an endogenous mirna as expression of endogenous targets will change. Interactions of mammalian retroviruses with cellular microrna. Micrornamediated interactions between host and hepatitis c virus. Cellular versus viral micrornas in hostvirus interaction. Multifaceted roles of micrornas in hostbacterial pathogen.
Integration of micrornatarget interactions along with their disease and drug associations yuanbin ru, katerina j. Epsteinbarr virusencoded micrornas as regulators in host. Flowchart describing the constructing of a virusmirna interactome. Ebv encoded mirbhrf11 potentiates viral lytic replication by downregulating host p53 in nasopharyngeal carcinoma. As a result, these mrna molecules are silenced, by one or more of the following. Role of virusencoded micrornas in avian viral diseases. Viruses, micrornas, and host interactions ncbi nih. Evidence is mounting that cellular mirnas play important roles in viral replication, either usurped by the virus to promote its replication or employed by the host to control viral infection by directly targeting the viral genome or by. Furthermore, viral infection can exert a profound impact on the cellular mirna expression profile, and several rna viruses have been reported to interact directly.
Interplay between hiv1 infection and host micrornas. Regarding to virus host interactions, recent advances have revealed that the complex interaction between viruses and host cells also involves mirnamediated rnasilencing pathways through which virus develop to exploit the biosynthetic machinery of host cells and elude the cellular defense. The role of rnai and micrornas in animal virus replication. Review micrornas in the interaction between host and bacterial pathogens claire maudeta, miguel manob,c, ana eulalioa. Infections of virulent and avirulent viruses differentially influenced. Genomewide profiling of micrornas reveals novel insights into the interactions between h9n2 avian influenza virus and avian dendritic cells 10 may 2018 oncogene, vol. In order to better understand beevirus interaction, we comparatively.
Micrornas in the host response to viral infections of. The study of mirnamediated host pathogen interactions has emerged in the last decade due to the important role that mirnas play in antiviral defense. It is currently difficult to determine the effect of oncogenic viruses on the global. Micrornas are 22 nucleotide rnas processed from rna hairpin structures. Considering the importance of micrornas mirnas in the regulation of essential processes in plant pathogen interactions, it is not surprising that, while plant mirna sequences counteract viral attack via antiviral rna silencing, viruses in turn have developed antihost defense mechanisms blocking these rna silencing pathways and establish a counterdefense.
Currently, two insect viruses, an ascovirus and a baculovirus, are. Evidence suggests that both virus and hosts encode micrornas. These regulatory rnas provide a unique level of posttranscriptional gene regulation that modulates a range of fundamental cellular processes. When cell is infected with virus, the cellular mirnas expression may be changed and affect both host and viral gene expression. Pdf micrornamediated interactions between host and. Micrornas in the host response to viral infections of veterinary importance mohamed samir1,2. Apr 30, 2012 micrornas mirnas are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. N2 one of the most significant recent advances in biomedical research has been the discovery of the.
This will help to reveal the molecular events involved in virushost interactions mediated by mirnas and their evolution in animals. Comprehensive modeling of microrna targets predicts functional nonconserved and noncanonical sites. According to study author howard weiner, since gut microbes play an important role in host metabolism and immunity as well as in disease, it is important to understand the mechanisms by which the microbiota is regulated by the host and to identify ways in which to manipulate the microbiome our findings reveal a host defense mechanism and highlight micrornas as a strategy for. Regulatory role of cellular and viral micrornas in insect. An inflammatory response is essential for combating invading pathogens. Profiling of epsteinbarr virusencoded micrornas in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs.
Rna viruses and the host microrna machinery nature. The outcomes of the two tools were merged, and mirna binding sites that were predicted by both tools were considered highly confident. The mirnacentered competitive viral and host rna network displays a crossregulation pattern between host mrnas and hcv genome. Vita also provides the virus annotations, virusinfected tissues and tissue specificity of host mirnas. Micrornas tend to synergistically control expression of genes. However, a systematic investigation of marine invertebrate mirnas that respond to virus infection has not yet been performed. Despite the fact that mirnasilencing mechanisms appear to be absent in some.
Modulation of the host mirna repertoire by salmonella infection was first described in mouse macrophages, where the nfb dependent mirnas mir. Identification of micrornas involved in the host response to. Developing a better comparative evolutionary understanding of pv gene products and their regulation is key to comprehending the life cycle of these pathogens. It has been shown that several avian viruses, mostly herpesviruses, encode a number of mirnas. In recent years, mirnas have been studied in order to discover antiviral ari drug targets as well as. During the past decade, mirnas have also been recognized for their role in the complex interplay between the host. Viral micrornas, host micrornas regulating viruses, and. Vita prediction of host micrornas targets on viruses hsls. Both cellular and virus encoded mirnas play important roles in virushost interactions. Role of microrna mirna has been highlighted in pathogen host interactions recently. Expression, avoidance and subversion by vertebrate viruses, abstract micrornas mirnas, which can be expressed in a celltype and tissuespecific manner, can influence the activities of genes that control cell growth and differentiation. They have been associated with numerous molecular mechanisms involving developmental, physiological and pathological changes of cells and tissues. The host transcripts could be targeted by micrornas expressed by either the host or virus as in the case of micrornas expressed by herpes simplex and epsteinbarr. Micrornas mirnas are small noncoding rnas that typically inhibit the translation and stability of messenger rnas mrnas, controlling genes involved in cellular processes such as inflammation, cellcycle regulation, stress response, differentiation, apoptosis, and migration.
Cellular mirna expression is profoundly influenced by viral infection, which can be attributed to both host antiviral defenses and viral factors altering the cellular environment. They appear to be involved in regulation of a wide range of cellular pathways that affect several biological processes such as development, the immune system, survival, metabolism and hostpathogen interactions. Homology to cellular micrornas is an additional method that viruses use to exploit the mirna system. Micrornamediated interactions between host and hepatitis. Hepatitis c virus hcv infection changes the expression of host mirnas in vitro and in vivo, while host micrornas mirnas in turn regulate hcv life cycle through directly binding to hcv rna and or indirectly targeting cellular mrnas. Currently, there is an incomplete understanding as to why only some infections lead to cancer.
An emerging concept of viral gene regulation is that many persistent. There are about 20,000 known human mrnas and 2,500. One of the most significant recent advances in biomedical research has been the discovery of the. In just a few short years micrornas have become firmly established as key molecular components of the cell in both normal and pathologic states 1. Novel micrornas and targets prediction in prrs virus genome. Thus, mirnas have been implicated in the regulation of virtually all signaling circuits within a cell, and their. Micrornas in the interaction between host and bacterial. Cellular microrna networks regulate host dependency of. Jun 12, 2015 poliovirus pv, the etiologic agent of paralytic poliomyelitis, is a human enterovirus with a singlestrand positive genomic rna that belongs to the picornaviridae family 1,2,3,4. To survive in the host cells, viruses have to adapt various strategies, which include the modulation of microrna mirna pathway through virusencoded mirnas to modulate the host cellular environment.
Some of the natural targets could be important for hiv1 infection 7,8,32. Viruses, micrornas, and host interactions pubmed central pmc. Micrornas mirnas are small rnas that play important roles in the regulation of gene expression. Expression and function of micrornas in viruses great and. Identification of micrornas in pcv2 subclinically infected. The role of micrornas in metabolic interactions between. The interactions of these small noncoding rnas in such primitive species have widereaching effects, from increasing viral and bacterial proliferation, better responses to stress, increased virulence, to manipulation of host immune responses to provide a more ideal environment for these pathogens to thrive. In humans, they regulate most proteincoding genes, including genes important in cancer and other diseases. The role of micrornas mirnas as small noncoding rnas in regulation of gene expression has been recognized. Certain viruses use micrornas mirnas to regulate the expression of their own genes, host genes, or both.
The most significant recent advance in biomedical research has been the discovery of the22nt long class of noncoding rnas designated as micrornas mirnas. Micrornas are much too short to code for protein and instead play important roles in regulating gene expression. For example, in addition to mir155, ebv induces mir146a expression in b cells. Some key functions of host mirnas and their mode of action. Their major role is in the posttranscriptional regulation of protein expression, and their involvement was demonstrated in normal and in pathological cellular processes. They are small, noncoding single stranded rnas, 1825 nucleotides nt in length. Crosstalk between long noncoding rnas and micrornas in health.
Author summary papillomaviruses pvs are causative agents of cancer. Hepatitis b virus hbv is a prototype member of the hepadnaviridae family and one of most common human pathogens worldwide. In combination with the increasing rate of new hcv infections, the lack of a current vaccine and or an effective treatment for this virus. To identify cellular mirnas involved in the host response to enterovirus 71 ev71 infection, we performed a comprehensive mirna profiling in ev71infected hep2 cells through deep sequencing. Several viruses, especially herpesviruses, also encode mirnas, and over 200 viral mirnas. Oct 11, 2006 micrornas mirnas are a new class of 1823 nucleotide long noncoding rnas that play critical roles in a wide spectrum of biological processes. This work was supported by grant ro1ai077746 from the national institutes of health, a national science foundation career award, a center for cancer research and prevention in texas grant, a burroughs wellcome investigators in pathogenesis award, and a ut austin institute for cellular and molecular biology fellowship to css. Q1 discovery of micrornas mirnas and their functions has led to a paradigm shift in our understanding of the regulation of gene expression, adding an extra layer of complexity for the mechanisms of gene expression. Dec, 2011 micrornas mirna are a class of noncoding rna that regulate the precise amounts of proteins expressed in a cell at a given time. Cancer in particular has been a major focus of microrna research over the past decade, and many studies have demonstrated the importance of micrornas in cancer biology through controlling expression of their target mrnas to facilitate tumor growth. Survey and summary cellular versus viral micrornas in host. Role of micrornas in insect hostmicroorganism interactions. Micrornas mirnas are a wellcharacterized class of small noncoding rnas that act as major posttranscriptional regulators of gene expression.
The how and where of plant micrornas author for correspondence. Chronic infection caused by hcv is considered one of the major causative agents of liver cirrhosis and hepatocellular carcinoma worldwide. Host factors as mirna targets and their role in hiv1 infection. Characterization of host micrornas that respond to dna virus infection in a crustacean. The discovery of rna interference and cellular micrornas mirnas has not only affected how biological research is conducted but also revealed an entirely new level of posttranscriptional gene. Export the merged interactome node list from cytoscape and remove all. Identification of virusencoded micrornas in divergent.
In vivo identification of interactions between active micrornas and target mrnas host teams harold cremer ibdm harold. There is extensive diversity in the functions of interactions in each class, depending on the mirna, the target, the cell. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. Cellular micrornas mirna belong to one such important class of sncrnas that regulate protein synthesis. Here, knowledge of virushost interactions may lead the way. A discussion of the physiologogical interplay between viruses and.
Micrornamediated interactions between host and hepatitis c virus article pdf available in world journal of gastroenterology 224. Radcliffe, russell bowler, spencer mahaffey, simona rossi, george a. Until now, 940 members of the family were identified in humans. The roles of micrornas and pirnas in virushost interactions. Micrornas, hepatitis c virus, host virus interaction, biomarker, therapeutic targets core tip. Micrornas mirnas are key posttranscriptional regulators of gene expression that are implicated in many processes of eukaryotic cells. This work also facilitates the comparisons between subtypes of viruses, such as influenza viruses, human liver viruses and the conserved regions between viruses. Recent reports also throw light into the role of micrornas as critical effectors in the intricate hostpathogen interaction networks. Micrornas mirnas are small noncoding rnas which play important roles in cellular process including response to viral infection. Nov 27, 2017 cellular micrornas mirnas have been shown to regulate hepatitis c virus hcv replication, yet a systematic interrogation of the repertoire of mirnas impacting hcv life cycle is lacking.
Interferon response and virushost interaction in aspect of. Survey and summary cellular versus viral micrornas in. The host mirnas downregulated in the mdvtransformed cell lines include mir155, mir223, mir150, mir451, and mir26a. Numerous conserved and divergent micrornas expressed by.
In the past decade, micrornas mirnas, a group of noncoding small rnas, have emerged as functionally significant regulatory. Regulation of mirna expression is increasingly recognized as a crucial part of the host response to infection by bacterial pathogens, as well as a novel. These effectors modulate various host cellular pathways necessary for productive infection 31, 32. For example, caenorhabditis elegans mirnas tend to be cleaved from precursors. This is in contrast to the rapid acquisition of adaptive mutations in response to drugs that target viral proteins, and emphasizes the benefits of targeting a host factor. These small noncoding rnas can contribute to the repertoire of host pathogen interactions during viral infection. Accumulating evidence demonstrates the differential expression of host mirnas upon infection by various microorganisms and the involvement of microorganismencoded mirnas in. Micrornas mirnas have appeared as important regulators of various biological processes including development, cancer, immunity, and hostmicroorganism interactions. Here we try to explore the intricacies of micrornamediated hostvirus crosstalk through a. Host defense or bacterial offense carmen aguilar,1 miguel mano,2 and ana eulalio1,3, micrornas are a class of small noncoding rnas that act as major posttranscriptional regulators of gene expression. Expression, avoidance and subversion by vertebrate.
Surprisingly, with the technology to combine crads with rnai at hand, arming crads with. Micrornas mirnas represent a class of small, 18 to 28nucleotidelong, noncoding rna molecules. Micrornas in the interaction between host and bacterial pathogens. Accumulating evidence demonstrates the differential expression of host mirnas upon infection by various microorganisms and the involvement of microorganismencoded mirnas in host manipulation.
Survey and summary cellular versus viral micrornas in hostvirus interaction zhumur ghosh1, bibekanand mallick1 and jayprokas chakrabarti1,2 1computational biology group, indian association for the cultivation of science, jadavpur, calcutta 700 032 and 2gyanxet, bf286, salt lake, calcutta 700 064, india. Our results revealed that 17 and 12 host mirnas were differentially. Again, we focused our efforts on targets for mir223 and mir29. Micrornas in the hostapicomplexan parasites interactions. Micrornas mirnas mark a new paradigm of rnadirected gene expression regulation in a wide spectrum of biological systems. Micrornas as important players in hosthepatitis b virus. In mammals, their involvement has been suggested in many cell processes and also in antiviral defence. They are currently recognized for their important role in the intricate interaction between host and. Despite the youth of the mirna field, mirna misexpression is known to occur in a range of human disease conditions and drugs based on modulating mirna expression. Both of these interactions serve to functionally sequester mir122 48, 49, 50. A microrna abbreviated mirna is a small noncoding rna molecule containing about 22 nucleotides found in plants, animals and some viruses, that functions in rna silencing and posttranscriptional regulation of gene expression. Geneticists still do not fully understand the interactions between the two types of rna. The host and virusencoded micrornas and their targets together thus form a novel regulatory layer of genetic interactions between the host and the virus.
40 1210 98 1411 824 1387 40 1195 334 141 1311 1128 1417 1350 245 1280 559 963 1539 968 1391 1008 258 1009 540 1363 455 1099 1362 720 452 347 1408 1176 511 274 1008 1445 159 719 1389