Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency.
Allen Sariah J,Rhode-Kurnow Antje,Mott Kevin R,Jiang Xianzhi,Carpenter Dale,Rodriguez-Barbosa J Ignacio,Jones Clinton,Wechsler Steven L,Ware Carl F,Ghiasi Homayon
Journal of virology
Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase cell survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency and reactivation by promoting cell survival and by helping the virus evade the host immune response. However, the mechanisms of these LAT activities are not well understood. We show here for the first time that one mechanism by which LAT enhances latency and reactivation appears to be by upregulating HVEM expression. HSV-1 latency/reactivation was significantly reduced in Hvem(-/-) mice, indicating that HVEM plays a significant role in HSV-1 latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency in vivo and also when expressed in vitro in the absence of other viral factors. This study suggests a mechanism whereby LAT upregulates HVEM expression potentially through binding of two LAT small noncoding RNAs to the HVEM promoter and that the increased HVEM then leads to downregulation of immune responses in the latent microenvironment and increased survival of latently infected cells. Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to be through increasing expression of HVEM.
10.1128/JVI.02467-13
Integrated analysis of mRNA and viral miRNAs in the kidney of Carassius auratus gibelio response to cyprinid herpesvirus 2.
Scientific reports
MicroRNAs (miRNAs) are small, non-coding single stranded RNAs that play crucial roles in numerous biological processes. Vertebrate herpesviruses encode multiple viral miRNAs that modulate host and viral genes. However, the roles of viral miRNAs in lower vertebrates have not been fully determined. Here, we used high-throughput sequencing to analyse the miRNA and mRNA expression profiles of Carassius auratus gibelio in response to infection by cyprinid herpesvirus 2 (CyHV-2). RNA sequencing obtained 26,664 assembled transcripts, including 2,912 differentially expressed genes. Based on small RNA sequencing and secondary structure predictions, we identified 17 CyHV-2 encoded miRNAs, among which 14 were validated by stem-loop quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and eight were validated by northern blotting. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNAs-mRNA pairs revealed diverse affected immune signalling pathways, including the RIG-I-like receptor and JAK-STAT pathways. Finally, we presented four genes involved in RIG-I-like pathways, including host gene IRF3, RBMX, PIN1, viral gene ORF4, which are negatively regulated by CyHV-2 encoded miRNA miR-C4. The present study is the first to provide a comprehensive overview of viral miRNA-mRNA co-regulation, which might have a key role in controlling post-transcriptomic regulation during CyHV-2 infection.
10.1038/s41598-017-14217-y
[Progress in microRNAs associated with major avian viruses].
Man Chaolai,Mu Weitao,Zhao Dongxue,Chang Yang
Sheng wu gong cheng xue bao = Chinese journal of biotechnology
Recently, avian viral diseases have become one of the main models to study mechanisms of viral infections and pathogenesis. The study of regulatory relationships and mechanisms between viruses and microRNAs has also become the focus. In this review, we briefly summarize the general situations of microRNAs encoded by avian herpesviruses. Also, we analyze the regulatory relationships between tumorigenicity of avian herpesviruses and microRNAs. Additionally, the possible applications for prevention and treatment of viral diseases (such as infectious bursal disease, avian influenza and avian leucosis) using the regulatory mechanisms of microRNAs are also discussed.
EBV miRNA expression profiles in different infection stages: A prospective cohort study.
Hartung Anita,Makarewicz Oliwia,Egerer Renate,Karrasch Matthias,Klink Anne,Sauerbrei Andreas,Kentouche Karim,Pletz Mathias W
PloS one
The Epstein-Barr virus (EBV) produces different microRNAs (miRNA) with distinct regulatory functions within the infectious cycle. These viral miRNAs regulate the expression of viral and host genes and have been discussed as potential diagnostic markers or even therapeutic targets, provided that the expression profile can be unambiguously correlated to a specific stage of infection or a specific EBV-induced disorder. In this context, miRNA profiling becomes more important since the roles of these miRNAs in the pathogenesis of infections and malignancies are not fully understood. Studies of EBV miRNA expression profiles are sparse and have mainly focused on associated malignancies. This study is the first to examine the miRNA profiles of EBV reactivation and to use a correction step with seronegative patients as a reference. Between 2012 and 2017, we examined the expression profiles of 11 selected EBV miRNAs in 129 whole blood samples from primary infection, reactivation, healthy carriers and EBV seronegative patients. Three of the miRNAs could not be detected in any sample. Other miRNAs showed significantly higher expression levels and prevalence during primary infection than in other stages; miR-BHRF1-1 was the most abundant. The expression profiles from reactivation differed slightly but not significantly from those of healthy carriers, but a specific marker miRNA for each stage could not be identified within the selected EBV miRNA targets.
10.1371/journal.pone.0212027
Pathogens Use and Abuse MicroRNAs to Deceive the Immune System.
Flór Thomas B,Blom Bianca
International journal of molecular sciences
Emerging evidence has demonstrated that microRNAs (miRs) play a role in the survival and amplification of viruses, bacteria and other pathogens. There are various ways in which pathogens can benefit from miR-directed alterations in protein translation and signal transduction. Members of the herpesviridae family have previously been shown to encode multiple miRs, while the production of miRs by viruses like HIV-1 remained controversial. Recently, novel techniques have facilitated the elucidation of true miR targets by establishing miR-argonaute association and the subsequent interactions with their cognate cellular mRNAs. This, in combination with miR reporter assays, has generated physiologically relevant evidence that miRs from the herpesviridae family have the potential to downregulate multiple cellular targets, which are involved in immune activation, cytokine signaling and apoptosis. In addition, viruses and bacteria have also been linked to the induction of host cellular miRs, which have the capacity to mitigate immune activation, cytokine signaling and apoptosis. Interfering with miR expression may be clinically relevant. In the case of hepatitis C infection, the cellular miR-122 is already targeted therapeutically. This not only exemplifies how important miRs can be for the survival of specific viruses, but it also delineates the potential to use miRs as drug targets. In this paper we will review the latest reports on viruses and bacteria that abuse miR regulation for their benefit, which may be of interest in the development of miR-directed therapies.
10.3390/ijms17040538
In vivo expression of human cytomegalovirus (HCMV) microRNAs during latency.
Meshesha Mesfin K,Bentwich Zvi,Solomon Semaria A,Avni Yonat Shemer
Gene
Viral encoded microRNAs play key roles in regulating gene expression and the life cycle of human herpes viruses. Latency is one of the hallmarks of the human cytomegalovirus (HCMV or HHV5) life cycle, and its control may have immense practical applications. The present study aims to identify HCMV encoded microRNAs during the latency phase of the virus. We used a highly sensitive real time PCR (RTPCR) assay that involves a pre-amplification step before RTPCR. It can detect HCMV encoded microRNAs (miRNAs) during latency in purified monocytes and PBMCs from HCMV IgG positive donors and in latently infected monocytic THP-1 cell lines. During the latency phase, only eight HCMV encoded microRNAs were detected in PBMCs, monocytes and in the THP-1 cells. Five originated from the UL region of the virus genome and three from the US region. Reactivation of the virus from latency, in monocytes obtained from the same donor, using dexamethasone restored the expression of all known HCMV encoded miRNAs including those that were absent during latency. We observed a shift in the abundance of the two arms of mir-US29 between the productive and latency stages of the viral life cycle, suggesting that the star "passenger" form of this microRNA is preferentially expressed during latency. As a whole, our study demonstrates that HCMV expresses during the latency phase, both in vivo and in vitro, only a subset of its microRNAs, which may indicate that they play an important role in maintenance and reactivation of latency.
10.1016/j.gene.2015.08.040
Viral MicroRNAs Identified in Human Dental Pulp.
Zhong Sheng,Naqvi Afsar,Bair Eric,Nares Salvador,Khan Asma A
Journal of endodontics
INTRODUCTION:MicroRNAs (miRs) are a family of noncoding RNAs that regulate gene expression. They are ubiquitous among multicellular eukaryotes and are also encoded by some viruses. Upon infection, viral miRs (vmiRs) can potentially target gene expression in the host and alter the immune response. Although prior studies have reported viral infections in human pulp, the role of vmiRs in pulpal disease is yet to be explored. The purpose of this study was to examine the expression of vmiRs in normal and diseased pulps and to identify potential target genes. METHODS:Total RNA was extracted and quantified from normal and inflamed human pulps (N = 28). Expression profiles of vmiRs were then interrogated using miRNA microarrays (V3) and the miRNA Complete Labeling and Hyb Kit (Agilent Technologies, Santa Clara, CA). To identify vmiRs that were differentially expressed, we applied a permutation test. RESULTS:Of the 12 vmiRs detected in the pulp, 4 vmiRs (including those from herpesvirus and human cytomegalovirus) were differentially expressed in inflamed pulp compared with normal pulp (P < .05). Using bioinformatics, we identified potential target genes for the differentially expressed vmiRs. They included key mediators involved in the detection of microbial ligands, chemotaxis, proteolysis, cytokines, and signal transduction molecules. CONCLUSIONS:These data suggest that miRs may play a role in interspecies regulation of pulpal health and disease. Further research is needed to elucidate the mechanisms by which vmiRs can potentially modulate the host response in pulpal disease.
10.1016/j.joen.2016.10.006