Mammalian alphaherpesvirus miRNAs

Jurak, Igor; Griffiths, Anthony John; Coen, Donald M.

doi:10.1016/j.bbagrm.2011.06.010

Cited by 32 publications

(26 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most of the current knowledge on latency has been obtained from studies of HSV-1 and HSV-2 in rodent models. In these settings, all LAT mutants that ablate LAT expression and the expression of multiple miRNAs can establish and maintain latency (18,(41)(42)(43). It was reported earlier that PrV mutants unable to express LAT and EP0 also were able to reach and persist in porcine trigeminal ganglia after intranasal infection (49).…”

Section: Discussionmentioning

confidence: 99%

“…By complete or partial hybridization, miRNAs induce target mRNA degradation and/or translational repression; thus, they serve key roles in the regulation of almost every important cellular process in multicellular eukaryotes (13)(14)(15). Given their small size, their lack of antigenicity, and their ability to inhibit the translation of specific mRNA species, miRNAs are thought to represent ideal tools for viruses to establish conditions permissive for viral replication, for the establishment of latency, or to allow rapid responses to changes in the environment, such as those that trigger reactivation from latency (16)(17)(18). The first viral miRNA was identified in Epstein-Barr virus (EBV), a gammaherpesvirus (19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Mahjoub

Dhorne–Pollet

Fuchs

et al. 2015

J Virol

View full text Add to dashboard Cite

The alphaherpesvirus pseudorabies virus (PrV) establishes latency primarily in neurons of trigeminal ganglia when only the transcription of the latency-associated transcript (LAT) locus is detected. Eleven microRNAs (miRNAs) cluster within the LAT, suggesting a role in establishment and/or maintenance of latency. We generated a mutant (M) PrV deleted of nine miRNA genes which displayed properties that were almost identical to those of the parental PrV wild type (WT) during propagation in vitro. IMPORTANCEThis study provides a thorough reference on the establishment of latency by PrV in its natural host, the pig. Our results corroborate the evidence obtained from the study of several LAT mutants of other alphaherpesviruses encoding miRNAs from their LAT regions. Neither PrV miRNA expression nor high LLT expression levels are essential to achieve latency in trigeminal ganglia. Once latency is established by PrV, the only remarkable differences are found in the pattern of host response. This indicates that, as in herpes simplex virus, LAT functions as an immune evasion locus. P seudorabies virus (PrV) is a porcine alphaherpesvirus. The genome of PrV is more than 142 kb in size and is characterized by the presence of 70 different coding genes plus the latency-associated transcript (LAT) locus (1, 2). PrV is the etiological agent of Aujeszky's disease, causing neurological, respiratory, and reproductive disease in the pig, its natural host. Despite successful vaccination campaigns and eradication of the virus from various countries, pseudorabies outbreaks still occur in swine populations worldwide, as recently reported from China (3). Because latent infection persists for lifetime after recovery from acute disease, pigs latently infected by PrV are a constant danger for virus reactivation, shedding, and spread in susceptible populations (4-6).A particular feature of herpesviruses is their ability to establish and maintain latent infections in which the virus genome circularizes and persists as an episome. As for other alphaherpesviruses, neurons in the trigeminal ganglia are the primary site of PrV latency (7). Over this period, transcription of viral lytic genes is repressed and transcription of the viral genome is restricted to the LAT locus overlapping the internal repeat sequence (IR) (8-10).RNAs of multiple sizes are transcribed from the strand opposite that encoding EP0 and IE180, which can be detected in infected Citation Mahjoub N, Dhorne-Pollet S, Fuchs W, Endale Ahanda M-L, Lange E, Klupp B, Arya A, Loveland JE, Lefevre F, Mettenleiter TC, Giuffra E. 2015. A 2.5-kilobase deletion containing a cluster of nine microRNAs in the latencyassociated-transcript locus of the pseudorabies virus affects the host response of porcine trigeminal ganglia during established latency.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Mahjoub

Dhorne–Pollet

Fuchs

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…An additional mechanism of antiapoptosis activity could lie in the encoding of viral microRNA within the LAT (Jurak et al 2012). Because of the compact nature of viral genomes in which viruses must package everything they need for productive infection, the encoding of microRNAs in nontranscribed regions and untranslated regions of exons can provide important regulatory elements at the transcriptional level (Boss and Renne 2010; Gottwein and Cullen 2008; Skalsky and Cullen 2010).…”

Section: Latent Hsv-1 Modulation Of Apoptosismentioning

confidence: 99%

Immunological control of herpes simplex virus infections

et al. 2013

View full text Add to dashboard Cite

Herpes simplex virus type 1 (HSV-1) is capable of causing a latent infection in sensory neurons that lasts for the lifetime of the host. The primary infection is resolved following the induction of the innate immune response that controls replication of the virus until the adaptive immune response can clear the active infection. HSV-1-specific CD8+ T cells survey the ganglionic regions containing latently infected neurons and participate in preventing reactivation of HSV from latency. The long-term residence and migration dynamics of the T cells in the trigeminal ganglia appear to distinguish them from the traditional memory T cell subsets. Recently described tissue resident memory (TRM) T cells establish residence and survive for long periods in peripheral tissue compartments following antigen exposure. This review focuses on the immune system response to HSV-1 infection. Particular emphasis is placed on the evidence pointing to the HSV-1-specific CD8+ T cells in the trigeminal belonging to the TRM class of memory T cells and the role of TRM cells in virus infection, pathogenesis, latency, and disease.

show abstract

“…Thus far, only a few targets of HSV miRNAs have been identified, and most of these are encoded from the strand opposite of that of an miRNA and thus are entirely complementary to the miRNA (37,83,84,91). HSV-1 miR-H1, the first HSV miRNA discovered, is expressed abundantly during productive (lytic) infection (15,38,42,91,92).…”

mentioning

confidence: 99%

Herpes Simplex Virus Is Equipped with RNA- and Protein-Based Mechanisms To Repress Expression of ATRX, an Effector of Intrinsic Immunity

Jurak

Silverstein

Sharma³

et al. 2012

J Virol

Self Cite

View full text Add to dashboard Cite

Intrinsic immunity is a first-line intracellular defense against virus infection, and viruses have evolved mechanisms to counteract it. During herpes simplex virus (HSV) infection, nuclear domain 10 (ND10) components localize adjacent to incoming viral genomes and generate a repressive environment for viral gene expression. Here, we found that the ND10 component, alpha-thalassemia/mental retardation syndrome X-linked (ATRX) protein, is predicted to be a target of HSV-1 miR-H1 and HSV-2 miR-H6. These microRNAs (miRNAs) share a seed sequence and are abundant during lytic infection. Mimics of both miRNAs could deplete endogenous ATRX, and an miR-H1 mimic could repress the expression of a reporter linked to the 3′ untranslated region of ATRX mRNA, identifying a cellular mRNA targeted by an HSV miRNA. Interestingly, ATRX protein and its mRNA were depleted in cells lytically infected with HSV, and ATRX protein was also depleted in cells infected with human cytomegalovirus. However, infection with an HSV-1 mutant lacking miR-H1 still resulted in ATRX depletion. This depletion was sensitive to a proteasome inhibitor and was largely ablated by a deletion of the gene encoding the immediate-early ICP0 protein. Additionally, a deletion of the gene encoding the tegument protein Vhs ablated most of the depletion of ATRX mRNA. Thus, HSV is equipped with multiple mechanisms to limit the expression of ATRX. As ATRX is implicated in repression of lytic viral gene expression, our results suggest roles for these different mechanisms during various phases of HSV infection.

show abstract

Mammalian alphaherpesvirus miRNAs

Cited by 32 publications

References 152 publications

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

A 2.5-Kilobase Deletion Containing a Cluster of Nine MicroRNAs in the Latency-Associated-Transcript Locus of the Pseudorabies Virus Affects the Host Response of Porcine Trigeminal Ganglia during Established Latency

Immunological control of herpes simplex virus infections

Herpes Simplex Virus Is Equipped with RNA- and Protein-Based Mechanisms To Repress Expression of ATRX, an Effector of Intrinsic Immunity

Contact Info

Product

Resources

About