Herpes simplex virus 1 miRNA sequence variations in latently infected human trigeminal ganglia

Brdovčak, Maja Cokarić; Zubković, Andreja; Ferenčić, Antun; Šoša, Ivan; Stemberga, Valter; Cuculić, Dražen; Rokić, Filip; Hackenberg, Michael; Jurak, Igor

doi:10.1016/j.virusres.2018.08.002

Cited by 11 publications

(9 citation statements)

References 63 publications

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“…Yet, not all herpesviruses express miRNAs. Varicella zoster virus (VZV) and Simian varicella virus (SVV), its non-human primate counterpart, have not been found to encode miRNAs [16,17,18], suggesting that other viral and/or host gene products could compensate for their roles. Indeed, a study by Pan et al (described in detail below) has shown that the host miRNA miR-138, which is expressed in herpes simplex virus 1 (HSV-1) latently infected cells, regulates the expression of ICP0, a viral protein that enhances the reactivation [19], and promotes the establishment of latency.…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus 1 Deregulation of Host MicroRNAs

Brdovčak

Zubković

Jurak

2018

ncRNA

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Viruses utilize microRNAs (miRNAs) in a vast variety of possible interactions and mechanisms, apparently far beyond the classical understanding of gene repression in humans. Likewise, herpes simplex virus 1 (HSV-1) expresses numerous miRNAs and deregulates the expression of host miRNAs. Several HSV-1 miRNAs are abundantly expressed in latency, some of which are encoded antisense to transcripts of important productive infection genes, indicating their roles in repressing the productive cycle and/or in maintenance/reactivation from latency. In addition, HSV-1 also exploits host miRNAs to advance its replication or repress its genes to facilitate latency. Here, we discuss what is known about the functional interplay between HSV-1 and the host miRNA machinery, potential targets, and the molecular mechanisms leading to an efficient virus replication and spread.

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Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus 1 Deregulation of Host MicroRNAs

Brdovčak

Zubković

Jurak

2018

ncRNA

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“…The expression of HSV-1 miRNAs in latently infected human ganglia has been comprehensively studied in only a few cases (10,46), and in contrast to studies in cultured cells and animal models, only a small subset of miRNAs has been detected (miR-H2 -miR-H8). Our study shows the expression of these miRNAs in all samples (Figure 1.)…”

Section: Results Mirna Sequencingmentioning

confidence: 99%

“…In our previous study, we identified particular sequence variants of HSV-1 miRNAs that could result from active posttranscriptional modifications by ADAR enzymes (46). To investigate this further, we analyzed the sequence variants of HSV-1 miRNAs in our dataset.…”

Section: Mir-h2 Is Hyperedited In Latently Infected Human Neuronsmentioning

confidence: 99%

HSV-1 miRNAs are posttranscriptionaly edited in latently infected human ganglia

Zubković

Gómez-Martín

Parchure

et al. 2023

Preprint

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Viruses use miRNAs to enable efficient replication, control host defense mechanisms, and regulate latent infection. Herpes simplex virus 1 (HSV-1) expresses multiple miRNAs, whose functions are largely unknown. The evolutionary conservation of many HSV-1 miRNAs in the closely related HSV-2 suggests their functional importance. miRNAs, similar to other transcripts, can undergo various posttranscriptional modifications that may affect their biogenesis, stability and targeting. To investigate whether ADAR mediated editing occurs in HSV-1 miRNAs, we sequenced samples from latently infected human ganglia. We show that one of the six HSV-1 miRNAs (miR-H2-H8) that define HSV-1 latency, miR-H2, exhibits A-to-I hyperediting within the miRNA seed sequence. We observed the same specific miR-H2 hyperediting phenomenon in miRNAs isolated from the ganglia of latently infected mice and, to a lesser extent, during productive infection in cultured cells. Curiously, we found no evidence of editing of the encoded HSV-2 homolog in latently infected mice or in cultured cells. The efficient loading of the edited miRNAs onto the RISC complex, indicates their ability to function as miRNAs. Therefore, to investigate the potential of the edited miRNA to alter mRNA targeting, we predicted the host and viral targets. Nucleotide substitution in the seed region significantly increased the number of potential host and viral targets. Most notably, ICP4, an essential viral protein, was predicted to be an additional target. Using transfection assays, we demonstrated that edited miRNAs have the potential to regulate ICP4 in addition to the previously identified target ICP0. Our study identifies a specific hyperedited HSV-1 mRNA, miR-H2, and highlights how the virus can use a single miRNA to target multiple transcripts during persistent, latent infection.

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“…HSV-1 expresses miRNAs from more than 20 loci (miR-H1-miR-H18 and miR-H26-H29), and often both strands of the miRNA duplex can be detected, indicating efficient utilization of the coding potential [44][45][46][47][48]. Most HSV-1 miRNAs were detected in productive infections, whereas only a small subset of miRNAs (miR-H2-H8) was detected in latently infected human ganglia [46,49]. Many HSV-1 miRNAs are conserved in HSV-2 and are in antisense to transcripts encoding important viral proteins.…”

Section: Adar and Herpesvirusesmentioning

confidence: 99%

RNA Editing-Dependent and -Independent Roles of Adenosine Deaminases Acting on RNA Proteins in Herpesvirus Infection—Hints on Another Layer of Complexity

Ivanišević,

Žilić,

Čunko

et al. 2023

Viruses

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The Adenosine Deaminases Acting on RNA (ADAR) catalyze the posttranscriptional deamination of adenosine residues to inosine in double-stranded RNAs (dsRNAs, A-to-I editing), preventing the overactivation of dsRNA sensor molecules and interferons. RNA editing is the cornerstone of innate immunity that distinguishes between self and non-self (virus), and it is essential for normal regulation of cellular homeostasis. Although much is already known about the role of ADAR proteins in RNA virus infection, the role of ADAR proteins in herpesvirus infection remains largely unexplored. In this review, we provide several lines of evidence from studies of different herpesviruses for another level of complexity in regulating the already intricate biphasic life cycle of herpesviruses.

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Herpes simplex virus 1 miRNA sequence variations in latently infected human trigeminal ganglia

Cited by 11 publications

References 63 publications

Herpes Simplex Virus 1 Deregulation of Host MicroRNAs

Herpes Simplex Virus 1 Deregulation of Host MicroRNAs

HSV-1 miRNAs are posttranscriptionaly edited in latently infected human ganglia

RNA Editing-Dependent and -Independent Roles of Adenosine Deaminases Acting on RNA Proteins in Herpesvirus Infection—Hints on Another Layer of Complexity

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