Host miRNAs Research Articles

The Etiology of COVID-19 in Silico by SARS-Cov-2 Infection with the Quantum Microrna Language-AI

Objective: Coronavirus disease 2019 (COVID-19) is complexed infectious disease caused by severe respiratory syndrome (SARS) human coronavirus 2 (CoV-2). We have previously shown that the microRNA (miRNA) entangling sorter (METS) analysis with quantum miRNA/miRNA language is available for the etiology investigation in silico of human virus-associated diseases. To investigate COVID-19 etiology, SARS-CoV-2 infection was simulated by METS algorithm with artificial intelligence (AI) machine learning (MIRAI). Materials and Methods: The information of coronavirus was extracted from database. Putative CoV-2 miRNAs were predicted by functionally analogy analysis. Statistical data was calculated by Prediction One. Results: The quantum miRNA immunity was observed in SARS-CoV-2 infection. Acute inflammation and viral infection mechanisms in COVID-19 were independently shown in host and viral miRNA networks according to the output of MIRAI. SARS-CoV-2 infection induced IL-6 upregulation by downregulation of miR-98-5p hub, and hypoxia was induced protein HIF1A suppression by viral miRNAs. C1q complement inhibition was tuned by viral miRNAs. Conclusion: We found in silico that COVID-19 might show IL-6 production by host miRNAs, and hypoxic vascular hypertension and hypocomplementemia-like symptom by viral miRNAs.

Differential expression of microRNAs in mud crab Scylla paramamosain in response to white spot syndrome virus (WSSV) infection

Till date numerous microRNAs (miRNAs) have been discovered from various organisms, including fish, shellfish and crustaceans. The miRNAs are known to regulate immune functions in crustaceans, but little is known about the role of miRNAs against viral infection in crab. We performed small RNA sequencing to characterize the differentially expressed miRNAs in WSSV infected Scylla paramamosain, in comparison to that in uninfected crab, at 2 h and 12 h post infection. In total, 24 host miRNAs were up-regulated and 25 host miRNAs were down-regulated in response to WSSV infection at 2 h post infection. And 27 host miRNAs were up-regulated and 30 host miRNAs were down-regulated in response to WSSV infection at 12 h post infection. Further, the gene ontology analysis revealed that many signaling pathways were mediated by these miRNAs. The integral component of membrane is the most important biological process and endocytosis pathway is the most important pathway, which indicates that endocytosis is very important for WSSV infection. This study is one important attempt at characterizing crab miRNAs that response to WSSV infection, and will help unravel the miRNA pathways involved in antiviral immunity of crab.

The Role of MicroRNAs in Parasitology.

MicroRNAs (miRNAs), as epigenetic regulators, are small non-coding RNAs regulating gene expression in eukaryotes at the post-transcriptional level to control biological functions. MicroRNAs play a role in development, physiology, infection, immunity and the complex life cycles of parasites. Also, parasite infection can alter host miRNA expression that might result in either parasite clearance or infection. Over the past 20 years, thousands of miRNAs have been identified in the nematode Caenorhabditis elegans and other parasites. Thus, miRNA pathways are potential targets for the diagnostic and therapeutic control of parasitic diseases. Here, we review the current status and potential functions of miRNAs related to protozoans, helminths, and arthropods.

The Role of MicroRNA in the Airway Surface Liquid Homeostasis.

Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host–pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.

Extracellular Vesicle-Contained microRNA of C. elegans as a Tool to Decipher the Molecular Basis of Nematode Parasitism.

Among the fundamental biological processes affected by microRNAs, small regulators of gene expression, a potential role in host-parasite communication is intriguing. We compared the miRNA complement of extracellular vesicles released by the free-living nematode Caenorhabditis elegans in culture to that of other adult parasitic nematodes. Expecting convergent functional roles for secreted miRNAs due to the common parasitic lifestyle of the organisms under investigation, we performed a miRNA sequence analysis as well as target search and pathway enrichment for potential mRNA targets within host immune functions. We found that the parasite miRNA seed sequences were more often identical to those of C. elegans, rather than to those of their hosts. However, we observed that the nematode-secreted miRNA fractions shared more often seed sequences with host miRNAs than those that are not found in the extracellular environment. Development and proliferation of immune cells was predicted to be affected several-fold by nematode miRNA release. In addition, we identified the AGE-RAGE signaling as a convergent targeted pathway by species-specific miRNAs from several parasitic species. We propose a multi-species comparative approach to differentiate those miRNAs that may have critical functions in host modulation, from those that may not. With our simple analysis, we put forward a workflow to study traits of parasitism at the miRNA level. This work will find even more resonance and significance, as an increasing amount of parasite miRNA collections are expected to be produced in the future.

Interactions Among Expressed MicroRNAs and mRNAs in the Early Stages of Fowl Adenovirus Aerotype 4-Infected Leghorn Male Hepatocellular Cells.

Hydropericardium-hepatitis syndrome (HHS) is caused by some strains of fowl adenovirus serotype 4 (FAdV-4). However, the mechanism of FAdV-4 entry is not well understood. Therefore, to investigate the changes in host cellular response at the early stage of FAdV-4 infection, a conjoint analysis of miRNA-seq and mRNA-seq was utilized with leghorn male hepatocellular (LMH) cells at 30, 60, and 120 min after FAdV-4 infection. In total, we identified 785 differentially expressed (DE) miRNAs and 725 DE mRNAs in FAdV-4-infected LMH cells. Most miRNAs and mRNAs, including gga-miR-148a-3p, gga-miR-148a-5p, gga-miR-15c-3p, CRK, SOCS3, and EGR1, have not previously been reported to be associated with FAdV-4 infection. The conjoint analysis of the obtained data identified 856 miRNA–mRNA pairs at three time points. The interaction network analysis showed that gga-miR-128-2-5p, gga-miR-7475-5p, novel_miR205, and TCF7L1 were located in the core of the network. Furthermore, the relationship between gga-miR-128-2-5p and its target OBSL1 was confirmed using a dual-luciferase reporter system and a real-time quantitative polymerase chain reaction assay. In vitro experiments revealed that both gga-miR-128-2-5p overexpression and OBSL1 loss of function inhibited FAdV-4 entry. These results suggested that gga-miR-128-2-5p plays an important role in FAdV-4 entry by targeting OBSL1. To the best of our knowledge, the present study is the first to analyze host miRNA and mRNA expression at the early stage of FAdV-4 infection; furthermore, the results of this study help to elucidate the molecular mechanisms of FAdV-4 entry.

Effects of gE/gI deletions on the miRNA expression of PRV-infected PK-15 cells

Pseudorabies virus (PRV) belongs to the Alphaherpesvirinae subfamily of Herpesviridae. PRV-induced pseudorabies is a highly contagious disease that has caused huge economic losses to the global swine industry. The PRV gE/gI gene deletion vaccine strain (Fa ΔgE/gI strain) constructed from the PRV Fa wild-type strain was shown to have a protective effect against infection. However, the interaction between PRV gE/gI genes and host miRNA needs further exploration, and little is known about the regulatory mechanisms of non-coding RNAs during PRV infection. miRNAs play a key regulatory role in viral infection and immune responses, so we analyzed the differential expression of miRNAs induced by the PRV Fa ΔgE/gI strain and Fa wild-type strain in the PK15 cell line. High-throughput sequencing reads were aligned to known Sus scrofa pre-miRNAs in the miRBase database. Target genes of differentially expressed miRNAs were predicted using the miRGen 3.0 database, then filtered miRNA target genes were subjected to Gene Ontology (GO) analysis and Search Tool for the Retrieval of Interacting Genes/ Proteins (STRING) analysis. Stem-loop quantitative real-time PCR was performed to confirm the accuracy of high-throughput sequencing data. In total, 387, 472, and 490 annotated and novel mature miRNAs were identified from PRV Fa ΔgE/gI strain-infected, Fa wild-type strain-infected, and non-infected PK-15 cells, respectively. Five PRV-encoded miRNAs were also identified. GO analysis showed that target genes of differentially expressed miRNAs in PRV Fa ΔgE/gI strain-infected and Fa wild-type strain-infected PK-15 cells were mainly involved in biological regulation and metabolic processes. STRING analysis showed that immune-related target genes of differentially expressed miRNAs in the Toll-like receptor signaling pathway, B cell receptor signaling pathway, T cell receptor signaling pathway, nuclear factor-κB signaling pathway, and transforming growth factor-β signaling pathway were interrelated. This is the first report of the small RNA transcriptome in PRV mutant wild-type strain-infected and Fa ΔgE/gI strain-infected porcine cell lines. Our findings will contribute to the prevention and treatment of PRV mutant strains.

Cellular microRNA, miR-1343-5p, modulates IFN-I responses to facilitate feline panleukopenia virus replication by directly targeting IRAK1 gene

Feline panleukopenia is an acute, highly contagious, and fatal infectious disease caused by feline panleukopenia virus (FPV) and has led to severe consequences on pets, economically important animals, and the wildlife industry. MicroRNAs (miRNAs) play significant roles in the host-pathogen interaction by modulating cellular factors expression which are essential for viral replication or host innate immune response to infection. However, the role of host miRNA response in FPV infection remains to be discovered. In this study, we screened nine host miRNAs associated with FPV infection that were previously implicated in innate immunity or antiviral functions. We found that miR-1343-5p overexpression strongly promoted FPV-BJ04 genomic DNA. Subsequently, the expression of host miR-1343-5p was upregulated by FPV-BJ04 infection in vitro and in vivo. In addition, we demonstrated that miR-1343-5p was a negative regulator of the IFN-I signaling pathway, thereby promoting FPV infection. Bioinformatic analysis combined with molecular biological assay indicated that interleukin-1 receptor-associated kinase 1 (IRAK1) is a putative target of miR-1343-5p. Collectively, our findings emphasize the importance of miR-1343-5p in host defense against FPV, thus, enhancing our understanding of its pathogenic mechanism.

Identification and characterization of hemocyte microRNAs in mud crab Scylla paramamosain in response to Vibrio parahemolyticus infection

The microRNAs (miRNAs) are known to regulate immune functions in crustaceans, but little is known about the role of miRNAs against bacterial infection. We performed small RNA sequencing to characterize the differentially expressed microRNAs in V. parahemolyticus infected crab, in comparison to that in control uninfected crab, at 12 h and 24 h post infection. In total, 23 host miRNAs were up-regulated in response to the infection and 23 host miRNAs were down-regulated at both the time-points. Among these miRNAs, miR-125, PC-3p-11,483, miR-281-5p, miR-10-3p and PC-5p-50,686 were significantly up-regulated by above 10 folds, and stem-loop RT-qPCR confirmed this result. Further, gene ontology analysis revealed that many signaling pathways, especially phagocytosis, were mediated by these miRNAs. Golgi apparatus and Magnesium ion binding are important biological processes, endocytosis and phagosome are important pathways in the immune response to V. parahemolyticus. This study is one important attempt at characterizing crab miRNAs that response to V. parahemolyticus infection, and will help unravel the miRNA pathways involved in antibacterial immunity of crab.

Circulating microRNAs as non-invasive biomarkers for hepatitis B virus liver fibrosis.

Viruses can alter the expression of host microRNAs (MiRNA s) and modulate the immune response during a persistent infection. The dysregulation of host MiRNA s by hepatitis B virus (HBV) contributes to the proinflammatory and profibrotic changes within the liver. Multiple studies have documented the differential regulation of intracellular and circulating MiRNA s during different stages of HBV infection. Circulating MiRNA s found in plasma and/or extracellular vesicles can integrate data on viral-host interactions and on the associated liver injury. Hence, the detection of circulating MiRNA s in chronic HBV hepatitis could offer a promising alternative to liver biopsy, as their expression is associated with HBV replication, the progression of liver fibrosis, and the outcome of antiviral treatment. The current review explores the available data on miRNA involvement in HBV pathogenesis with an emphasis on their potential use as biomarkers for liver fibrosis.

MicroRNA Involvement in Signaling Pathways During Viral Infection.

The study of miRNAs started in 1993, when Lee et al. observed their involvement in the downregulation of a crucial protein known as LIN-14 in the nematode Caenorhabditis elegans. Since then, great progress has been made regarding research on microRNAs, which are now known to be involved in the regulation of various physiological and pathological processes in both animals and humans. One such example is represented by their interaction with various signaling pathways during viral infections. It has been observed that these pathogens can induce the up-/downregulation of various host miRNAs in order to elude the host’s immune system. In contrast, some miRNAs studied could have an antiviral effect, enabling the defense mechanisms to fight the infection or, at the very least, they could induce the pathogen to enter a latent state. At the same time, some viruses encode their own miRNAs, which could further modulate the host’s signaling pathways, thus favoring the survival and replication of the virus. The goal of this extensive literature review was to present how miRNAs are involved in the regulation of various signaling pathways in some of the most important and well-studied human viral infections. Further on, knowing which miRNAs are involved in various viral infections and what role they play could aid in the development of antiviral therapeutic agents for certain diseases that do not have a definitive cure in the present. The clinical applications of miRNAs are extremely important, as miRNAs targeted inhibition may have substantial therapeutic impact. Inhibition of miRNAs can be achieved through many different methods, but chemically modified antisense oligonucleotides have shown the most prominent effects. Though scientists are far from completely understanding all the molecular mechanisms behind the complex cross-talks between miRNA pathways and viral infections, the general knowledge is increasing on the different roles played by miRNAs during viral infections.

Expression profiling of miR-146a-3p and miR-1343 with their target genes after classical swine fever vaccination

The expression profiling of the miRNAs, ssc-miR-146a- 3p and ssc-miR-1343 in the PBMCs of classical swine fever (CSF) vaccinated crossbred pigs were investigated on 7 days post vaccination (7 dpv) as compared to unvaccinated pigs. It was observed that ssc-miR-146a-3p was up-regulated (1.243 Log2 FC) and ssc-miR-1343 was down-regulated (-1.63 Log2 FC) on 7 dpv compared to unvaccinated crossbred pigs which were in concordance with earlier report of miRNA Seq expression profiling. Two target genes, (CD86 for ssc-miR-146a-3p and IFIT1 for ssc-miR-1343) were validated by qRT-PCR and were also found to be in concordance with miRNA expression profile. The CD86 was downregulated with log2 fold changes -5.99, whereas the IFIT1 was upregulated with log2 fold changes 3.19 at 7 dpv. Both of these miRNA was actively involved in cell mediated immune response at 7dpv after CSF vaccination. The CSF vaccine virus triggered the expression of host miRNAs and its target mRNA and enriched immune system processes/pathways.

Role of Viral and Host microRNAs in Immune Regulation of Epstein-Barr Virus-Associated Diseases.

Epstein-Barr virus (EBV) is an oncogenic human herpes virus that was discovered in 1964. Viral non-coding RNAs, such as BamHI-A rightward fragment-derived microRNAs (BART miRNAs) or BamHI-H rightward fragment 1-derived miRNAs (BHRF1 miRNA) in EBV-infected cells have been recently reported. Host miRNAs are also upregulated upon EBV infection. Viral and host miRNAs are important in maintaining viral infection and evasion of host immunity. Although miRNAs in EBV-infected cells often promote cell proliferation by targeting apoptosis or cell cycle, this review focuses on the regulation of the recognition of the host immune system. This review firstly describes the location and organization of two clusters of viral miRNAs, then describes evasion from host immune surveillance systems by modulating viral gene expression or inhibiting innate and acquired immunity by viral miRNAs as well as host miRNAs. Another topic is the enigmatic depletion of viral miRNAs in several types of EBV-infected tumor cells. Finally, this review introduces the strong correlation of nasopharyngeal cancer cases with a newly identified single nucleotide polymorphism that enhances BART miRNA promoter activity.

Immune-related miRNA-mRNA regulation network in the livers of DHAV-3-infected ducklings

BackgroundDuck hepatitis A virus type 3 (DHAV-3) is one of the most harmful pathogens in the duck industry. However, the molecular mechanism underlying DHAV-3 infection in ducklings remains poorly understood. To study the genetic regulatory network for miRNA-mRNA and the signaling pathways involved in DHAV-3 infection in ducklings, we conducted global miRNA and mRNA expression profiling of duckling liver tissues infected with lethal DHAV-3 by high-throughput sequencing.ResultsWe found 156 differentially expressed miRNAs (DEMs) and 7717 differentially expressed genes (DEGs) in livers of mock-infected and DHAV-3-infected duckling. A total of 19,606 miRNA-mRNA pairs with negatively correlated expression patterns were identified in miRNA-mRNA networks constructed on the basis of these DEMs and DEGs. Moreover, immune-related pathways, including the cytokine-cytokine receptor interaction, apoptosis, Toll-like receptor, Jak-STAT, and RIG-I-like receptor signaling pathway, were significantly enriched through analyzing functions of mRNAs in the network in response to DHAV-3 infection. Furthermore, apl-miR-32-5p, apl-miR-125-5p, apl-miR-128-3p, apl-miR-460-5p, and novel-m0012-3p were identified as potential regulators in the immune-related signaling pathways during DHAV-3 infection. And some host miRNAs were predicted to target the DHAV-3 genome.ConclusionsThis is the first integrated analysis of miRNA and mRNA in DHAV-3-infected ducklings. The results indicated the important roles of miRNAs in regulating immune response genes and revealed the immune related miRNA-mRNA regulation network in the DHAV-3-infected duckling liver. These findings increase our knowledge of the roles of miRNAs and their target genes in DHAV-3 replication and pathogenesis. They also aid in the understanding of host-virus interactions.

Exosomal miRNAs: novel players in viral infection.

Exosomes are secreted nanovesicles that are able to transfer their cargo (such as miRNAs) between cells. To determine to what extent exosomes and exosomal miRNAs are involved in the pathogenesis, progression and diagnosis of viral infections. The scientific literature (PubMed and Google Scholar) was searched from 1970 to 2019. The complex biogenesis of exosomes and miRNAs was reviewed. Exosomes contain both viral and host miRNAs that can be used as diagnostic biomarkers for viral diseases. Viral proteins can alter miRNAs, and conversely miRNAs can alter the host response to viral infections in a positive or negative manner. It is expected that exosomal miRNAs will be increasingly used for diagnosis, monitoring and even treatment of viral infections.

Plasma extracellular microRNAs are related to AIDS/cerebral toxoplasmosis co-infection.

This study investigated the potential of five miRNA candidates for cerebral toxoplasmosis/HIV co-infection (CT/HIV) biomarkers. miR-155-5p, miR-146a-5p, miR-21-5p, miR-125b-5p and miR-29c-3p were tested in 79 plasma divided into groups: 32 CT/HIV patients; 27 individuals with asymptomatic toxoplasmosis (AT); and 20 individuals seronegative for toxoplasmosis (NC). From each was collected peripheral blood/EDTA for laboratory diagnosis. Blood cells for DNA extractions (molecular diagnosis), plasma for RNA extractions (gene expression) and ELISA (serological diagnosis). miRNA expression was performed by qPCR, and values were expressed in Relative Quantification (RQ). Among the five miRNAs, miR-21-5p and miR-146a-5p were up-expressed in CT/HIV group when compared with AT and NC groups. RQ means for miR-21-5p and miR-146a-5p in CT/HIV group were 3.829 and 2.500, while in AT group, were 1.815 and 1.661, respectively. Differences between 3 groups were statistically significant (Kruskal-Wallis ANOVA test), as well as CT/HIV and AT groups (Mann-Whitney test). Plasma of CT/HIV and AT groups expressed similar levels of miR-29c-3p, miR-155-5p and miR-125b-5p. As NC group was different of CT/HIV and AT groups, differences between three groups were statistically significant (Kruskal-Wallis ANOVA test). No difference was shown between CT/HIV and AT groups (Mann-Whitney test). These results suggest the host miRNAs modulation by Toxoplasma gondii.

The Quantum microRNA Immunity in Human Virus-Associated Diseases: Virtual Reality of HBV, HCV and HIV-1 Infection, and Hepatocellular Carcinogenesis with AI Machine Learning

Objectives: Since virus-related hepatocellular carcinoma (HCC) is quite complexed, the etiology of virus-associated HCC is remained unclear. We have previously shown that the microRNA (miRNA) entangling sorter (METS) analysis with quantum miRNA/miRNA language is available for the etiology investigation in silico from miRNA biomarker panels of human cancers to predict carcinogenesis. To further investigate the etiology of human virus-associated diseases on the stage minus one (zero), host-virus miRNA interactions were investigated by computer simulation on METS analysis with artificial intelligence (AI) machine learning (MIRAI). Materials and Methods: The information of the miRNA biomarker panels in hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) infection, virus-related fibrosis (cirrhosis), and virus-associated HCCs was extracted from database. The miRNA hub in the panels was selected by both protein/protein interaction and carcinogenic protein function. The statistical analysis upon tumorigenesis was calculated by Prediction One. Results: The etiology of infection, fibrosis or HCC was simulated by METS analysis with host miRNAs and viral miRNAs. Quite different strategy was shown as the host defense against HBV, HCV and HIV-1 infection under controlled by host miRNAs and viral mRNAs. HBV and HIV-1 was defensed by cell death through shutdown and cell cycle arrest, respectively. HCV was prevented by inhibition of virus production. Carcinogenesis by HBV was induced by repeated wound-healing in fibrosis (cirrhosis) programmed by host miRNA information, and host and viral miRNAs were implicated in tumorigenic activity upon HCV infection. Conclusions: We found the third host defense neomechanism, named ‘the quantum miRNA immunity’ against human virus-related diseases.

MRNA and miRNA profiling of Zika virus-infected human umbilical cord mesenchymal stem cells identifies miR-142-5p as an antiviral factor

ABSTRACT Zika virus (ZIKV) infection during pregnancy is associated with congenital brain abnormalities, a finding that highlights the urgent need to understand mother-to-fetus transmission mechanisms. Human umbilical cord mesenchymal stem cells (hUCMSCs) are susceptible to ZIKV infection but the underlying mechanisms of viral susceptibility remain largely unexplored. In this study, we have characterized and compared host mRNA and miRNA expression profiles in hUCMSCs after infection with two lineages of ZIKV, African (MR766) and Asian (PRVABC59). RNA sequencing analysis identified differentially expressed genes involved in anti-viral immunity and mitochondrial dynamics following ZIKV infection. In particular, ZIKV-infected hUCMSCs displayed mitochondrial elongation and the treatment of hUCMSCs with mitochondrial fission inhibitor led to a dose-dependent increase in ZIKV gene expression and decrease in anti-viral signalling pathways. Moreover, small RNA sequencing analysis identified several significantly up- or down-regulated microRNAs. Interestingly, miR-142-5p was significantly downregulated upon ZIKV infection, whereas cellular targets of miR-142-5p, IL6ST and ITGAV, were upregulated. Overexpression of miR-142-5p resulted in the suppression of ZIKV replication. Furthermore, blocking ITGAV expression resulted in a significant suppression of ZIKV binding to cells, suggesting a potential role of ITGAV in ZIKV entry. In conclusion, these results demonstrate both common and specific host responses to African and Asian ZIKV lineages and indicate miR-142-5p as a key regulator of ZIKV replication in the umbilical cords.

MiR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling.

In response to viral infection, host cells activate various antiviral responses to inhibit virus replication. While feline herpesvirus 1 (FHV-1) manipulates the host early innate immune response in many different ways, the host could activate the antiviral response to counteract it through some unknown mechanisms. MicroRNAs (miRNAs) which serve as a class of regulatory factors in the host, participate in the regulation of the host innate immune response against virus infection. In this study, we found that the expression levels of miR-26a were significantly upregulated upon FHV-1 infection. Furthermore, FHV-1 infection induced the expression of miR-26a via a cGAS-dependent pathway, and knockdown of cellular cGAS significantly blocked the expression of miR-26a induced by poly (dA:dT) or FHV-1 infection. Next, we investigated the biological function of miR-26a during viral infection. miR-26a was able to increase the phosphorylation of STAT1 and promote type I IFN signaling, thus inhibiting viral replication. The mechanism study showed that miR-26a directly targeted host SOCS5. Knockdown of SOCS5 increased the phosphorylation of STAT1 and enhanced the type I IFN-mediated antiviral response, and overexpression of suppressor of the cytokine signalling 5 (SOCS5) decreased the phosphorylation of STAT1 and inhibited the type I IFN-mediated antiviral response. Meanwhile, with the knockdown of SOCS5, the upregulated expression of phosphorylated STAT1 and the anti-virus effect induced by miR-26a were significantly inhibited. Taken together, our data demonstrated a new strategy of host miRNAs against FHV-1 infection by enhancing IFN antiviral signaling.

Endosomal TLR-8 Senses microRNA-1294 Resulting in the Production of NFḱB Dependent Cytokines.

The primary function of toll-like receptor 8 (TLR-8) is the detection of viruses and other microbial pathogens. Recent evidence suggests that TLR-8 also senses host microRNAs (miRNAs) and implicate TLR-8 in autoimmune disorders. This study examined the interaction between miR-1294 and TLR-8. We first performed a BLAST search to identify miRNAs with the same sequences as two core motifs of miR-1294. Next, we examined NFḱB activation induced by the binding of miR-1294 mimic to endosomal TLR-8. HEK-Blue™ hTLR-8 cells (Invivogen), a HEK293 cell line co-transfected with human TLR-8 gene, were incubated with miR-1294 mimic. A TLR-8 agonist ssRNA40, was used as a positive control. Using the same experimental set up, we also examined the effects of miR-1294 and its two core motifs (Integrated DNA Technologies) on IL-8, IL-1β, and TNFα. Data were analyzed using t-test or one-way ANOVA and Dunnets post-hoc test. Using miRCarta we identified 29 other mature human miRNAs or their precursors which contain the same core motifs as miR-1294. Our data show that miR-1294 activates NFḱB in cells expressing TLR-8 (p < 0.05). miR-1294, and its core motifs induce expression of IL-8, IL-1β, and TNFα via TLR8 activation (p < 0.05). This constitutes a novel mechanism by which endosomal TLR-8 senses host miRNAs resulting in the release of pro-inflammatory cytokines and thus potentially contributing to autoimmune disorders.