Identification and Analysis of Expression of Novel MicroRNAs of Murine Gammaherpesvirus 68

Zhu, Jiang; Strehle, Martin; Frohn, Anne; Kremmer, Elisabeth; Höfig, Kai P.; Meister, Gunter; Adler, Heiko

doi:10.1128/jvi.01119-10

Cited by 45 publications

(48 citation statements)

References 51 publications

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“…miR-M1-7-3p conferred the greatest reduction and miR-M1-12, the least. This is consistent with the reported abundance of each miRNA detected during infection in previous studies (Reese et al, 2010; Zhu et al, 2010). Within the cells transfected with the pLE-WT plasmid, we saw a similar pattern of reduction.…”

Section: Resultssupporting

confidence: 93%

“…Locations of the γHV68 encoded miRNA genes are shown as dashed lines and labeled miR-M1-(1-15). *miR-M1-11 is the only γHV68 miRNA that is not directly embedded within a predicted TMER primary transcript (Reese et al, 2010; Zhu et al, 2010). The miRNA genes are labeled here as found on the miRBase website (Kozomara and Griffiths-Jones, 2011).…”

Section: Highlightsmentioning

confidence: 99%

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A conserved RNA polymerase III promoter required for gammaherpesvirus TMER transcription and microRNA processing

Diebel

Claypool

Dyk

2014

Gene

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Canonical RNA polymerase III (pol III) type 2 promoters contain a single A and B box and are well documented for their role in tRNA and SINE transcription in eukaryotic cells. The genome of Murid herpesvirus 4 (MuHV-4) contains eight polycistronic tRNA-microRNA encoded RNA (TMER) genes that are transcribed from a RNA pol III type 2-like promoter containing triplicated A box elements. Here, we demonstrate that the triplicated A box sequences are required in their entirety to produce functional MuHV-4 miRNAs. We also identify that these RNA pol III type 2-like promoters are conserved in eukaryotic genomes. Human and mouse predicted tRNA genes containing these promoters also show enrichment of alternative RNA pol III transcription termination sequences and are predicted to give rise to longer tRNA primary transcripts.

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Section: Resultssupporting

confidence: 93%

Section: Highlightsmentioning

confidence: 99%

A conserved RNA polymerase III promoter required for gammaherpesvirus TMER transcription and microRNA processing

Diebel

Claypool

Dyk

2014

Gene

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“…S3a and b). Treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was used as a positive control for the induction of virus reactivation in S11 B cells [31], and treatment with lipopolysaccharide (LPS) in ANA-1/MHV-68 macrophages [32]. Exposure to 50 μg/ml NP resulted in an increase in virus titers in the supernatants of both cell lines, indicating virus reactivation.…”

Section: Resultsmentioning

confidence: 99%

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

et al. 2017

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BackgroundInhalation of environmental (nano) particles (NP) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. We hypothesized that NP-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage.ResultsTo test this hypothesis, we applied different NP to cells or mice latently infected with murine gammaherpesvirus 68 (MHV-68) which provides a small animal model for the study of gammaherpesvirus-pathogenesis in vitro and in vivo. In vitro, NP-exposure induced expression of the typically lytic viral gene ORF50 and production of lytic virus. In vivo, lytic viral proteins in the lung increased after intratracheal instillation with NP and elevated expression of the viral gene ORF50 could be detected in cells from bronchoalveolar lavage. Gene expression and metabolome analysis of whole lung tissue revealed patterns with striking similarities to acute infection. Likewise, NP-exposure of human cells latently infected with Epstein-Barr-Virus also induced virus production.ConclusionsOur results indicate that NP-exposure of persistently herpesvirus-infected cells – murine or human – restores molecular signatures found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a combination which might finally result in tissue damage and pathological alterations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0181-1) contains supplementary material, which is available to authorized users.

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“…For the IGB output, the coding sequence (CDS) and mRNA tracks were created on the basis of the sequence with NCBI accession number NC_001826. Additional coordinates for the spliced transcript structures are as previously indicated for M2 (16), ORF50 (29), ORF57 (56), ORF72 (3,4), ORF73 (4,12), the noncoding expressed genomic regions (EGRs) (40), and tRNA-miRNA (69,93).…”

mentioning

confidence: 99%

Tiled Microarray Identification of Novel Viral Transcript Structures and Distinct Transcriptional Profiles during Two Modes of Productive Murine Gammaherpesvirus 68 Infection

Cheng

Zhi

Santana

et al. 2012

J Virol

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cWe applied a custom tiled microarray to examine murine gammaherpesvirus 68 (MHV68) polyadenylated transcript expression in a time course of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently infected B cell line. During de novo infection, all open reading frames (ORFs) were transcribed and clustered into four major temporal groups that were overlapping yet distinct from clusters based on the phorbol ester-stimulated B cell reactivation time course. High-density transcript analysis at 2-h intervals during de novo infection mapped gene boundaries with a 20-nucleotide resolution, including a previously undefined ORF73 transcript and the MHV68 ORF63 homolog of Kaposi's sarcoma-associated herpesvirus vNLRP1. ORF6 transcript initiation was mapped by tiled array and confirmed by 5= rapid amplification of cDNA ends. The ϳ1.3-kb region upstream of ORF6 was responsive to lytic infection and MHV68 RTA, identifying a novel RTA-responsive promoter. Transcription in intergenic regions consistent with the previously defined expressed genomic regions was detected during both types of productive infection. We conclude that the MHV68 transcriptome is dynamic and distinct during de novo fibroblast infection and upon phorbol ester-stimulated B cell reactivation, highlighting the need to evaluate further transcript structure and the context-dependent molecular events that govern viral gene expression during chronic infection. Murine gammaherpesvirus 68 (MHV68; also known as ␥HV68 or murid herpesvirus 4) infection of mice is a model pathogenesis system for gammaherpesviruses such as Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/ HHV-8) and Epstein-Barr virus (EBV) (5, 20). The life cycles of these lymphotropic and transforming viruses in the host involve the initial transit across a mucosal barrier to gain access to and establish latency in a leukocyte reservoir, followed by intermittent reactivation and dissemination to the mucosal surfaces for spread to new hosts (32,74,77,82).Replication at the site of primary infection impacts MHV68 dissemination and latency establishment in secondary lymphoid tissues of mice. The absence of proteins essential for lytic replication, such as the viral transactivator ORF50/mRTA (61) and the ORF6/single-stranded DNA-binding protein (ssDBP) (49), or the inhibition of viral DNA replication by the administration of cidofovir (62) impairs the establishment of latency in the splenic B cell compartment. In addition, virus replication at the mucosa triggers the innate and adaptive immune responses critical for host control (6,45,72,73). These responses might play a critical role in the recruitment and activation of target cells such as dendritic cells that precede dissemination to distal reservoirs, such as splenic B cells and peritoneal macrophages (5, 25). Thus, the lytic gene expression program in newly infected cells that are permissive for productive infection is an important aspect of pathogenesis.Reactivation from latency is a...

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Identification and Analysis of Expression of Novel MicroRNAs of Murine Gammaherpesvirus 68

Cited by 45 publications

References 51 publications

A conserved RNA polymerase III promoter required for gammaherpesvirus TMER transcription and microRNA processing

A conserved RNA polymerase III promoter required for gammaherpesvirus TMER transcription and microRNA processing

Nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection

Tiled Microarray Identification of Novel Viral Transcript Structures and Distinct Transcriptional Profiles during Two Modes of Productive Murine Gammaherpesvirus 68 Infection

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