Marek's disease virus: from miasma to model

Osterrieder, Nikolaus; Kamil, Jeremy P.; Schumacher, Daniel; Tischer, B. Karsten; Trapp, Sascha

doi:10.1038/nrmicro1382

Cited by 355 publications

(315 citation statements)

References 118 publications

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“…The primers specific for GAPDH were described (36), whereas the gB-and U L 36/MDV USP -specific primers are shown in SI 19 ) chickens were obtained from Cornell University's departmental f locks and housed in isolation units. Water and food were provided ad libitum.…”

Section: Methodsmentioning

confidence: 99%

“…It is a major source of concern for the poultry industry and necessitates vaccination of chicken flocks in ovo or shortly after hatching (17)(18)(19). The severity of the symptoms and their clockwork timing, as well as the availability of the natural host, make MDV an ideal model to assess the importance of the viral USP for alphaherpesvirus pathogenesis in vivo.…”

mentioning

confidence: 99%

“…The severity of the symptoms and their clockwork timing, as well as the availability of the natural host, make MDV an ideal model to assess the importance of the viral USP for alphaherpesvirus pathogenesis in vivo. The course of infection includes lytic replication, then latency, followed by reactivation and the formation of massive T cell lymphomas in multiple organs (18)(19)(20). We undertook the generation of an MDV mutant that lacks the USP activity to address its role in pathogenicity.…”

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confidence: 99%

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A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation

Jarosinski

Kattenhorn

Kaufer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The herpesvirus ubiquitin-specific protease (USP) family, whose founding member was discovered as a protease domain embedded in the large tegument protein of herpes simplex virus 1 (HSV-1), is conserved across all members of the Herpesviridae. Whether this conservation is indicative of an essential function of the enzyme in vivo has not yet been established. As reported here, USP activity is conserved in Marek's disease virus (MDV), a tumorigenic alphaherpesvirus. A single amino acid substitution that abolishes the USP activity of the MDV large tegument protein diminishes MDV replication in vivo, and severely limits the oncogenic potential of the virus. Expression of the USP transcripts in MDV-transformed cell lines further substantiates this hypothesis. The herpesvirus USP thus appears to be required not only to maintain a foothold in the immunocompetent host, but also to contribute to malignant outgrowths.chicken ͉ deubiquitinating enzyme ͉ herpes ͉ Marek's disease virus T he ubiquitin-proteasome system controls cytosolic proteolysis, certain aspects of transcription, antigen presentation via major histocompatibility complex (MHC) class I products, and the trafficking of surface-exposed receptors (1-5). As for many other posttranslational modifications, both ubiquitin conjugation and its reversal by ubiquitin-specific proteases (USPs) determine the biological outcome of the reaction. The enzyme families that catalyze ubiquitin conjugation and removal are quite diverse (6-9). Consequently, bioinformatic analysis is not always adequate to identify novel USPs. To target such enzymes biochemically, we developed activity-based probes for USPs and enzymes that act on ubiquitin-like modifiers (10). These probes are equipped with an affinity handle to allow retrieval and identification of the enzymes targeted by the electrophilic warhead installed at the probe's carboxyl terminus.Through the use of one of these probes, HA-ubiquitin vinylmethylester (HA-UbVME), we identified the large tegument protein of herpes simplex virus 1 (HSV-1), viral protein (VP) 1/2, encoded by the unique-long (U L ) 36 gene, as the source of an active USP. Its sequence showed no obvious similarity to known eukaryotic USPs and failed to yield an obvious signature of residues diagnostic of known cysteine protease families. Nonetheless, sequence comparisons across the Herpesviridae show the presence of a few absolutely conserved residues (Cys, Asp, His, Glu), all of which are consistent with involvement in a potential thiol protease active site. We have, meanwhile, confirmed both the mechanism of action of such ubiquitin-based probes (11)(12)(13)(14)(15) and the identity of the viral cysteine protease domain as an authentic USP by crystallographic analysis of the homologous segment of the murine cytomegalovirus (MCMV) M48 protein (16). Notwithstanding the conservation of the identified USP activity in all herpesviruses, we do not know whether this activity makes a contribution to the replicative success and pathogenicity of herpesviruses in vivo...

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation

Jarosinski

Kattenhorn

Kaufer

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Marek's disease (MD) is a α-herpesvirus-induced T-cell lymphoma in chickens [1,2]. MD historically caused devastating losses to the Received: July 18, 2017; Accepted: August 10, 2017; Published: August 14, 2017 …”

Section: Introductionmentioning

confidence: 99%

Genomic Variation between Genetic Lines of White Leghorns Differed in Resistance to Marek’s Disease

Xie¹,

Chang²,

Dong³

et al. 2017

J Clin Epigenet

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“…vTR was identified in the genome of Marek's disease virus (MDV), a herpesvirus that induces T-lymphomas in its natural host, the chicken [28,29]. The involvement of vTR in virally induced tumorigenesis has been clearly established [30,31].…”

Section: Introductionmentioning

confidence: 99%

The human telomerase catalytic subunit and viral telomerase RNA reconstitute a functional telomerase complex in a cell-free system, but not in human cells

Trapp-Fragnet¹,

Marie-Egyptienne²,

Fakhoury³

et al. 2012

Cellular and Molecular Biology Letters

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Abstract:The minimal vertebrate telomerase enzyme is composed of a protein component (telomerase reverse transcriptase, TERT) and an RNA component (telomerase RNA, TR). Expression of these two subunits is sufficient to reconstitute telomerase activity in vitro, while the formation of a holoenzyme comprising telomerase-associated proteins is necessary for proper telomere length maintenance. Previous reports demonstrated the high processivity of the human telomerase complex and the interspecies compatibility of human TERT (hTERT). In this study, we tested the function of the only known viral telomerase RNA subunit (vTR) in association with human telomerase, both in a cell-free system and in human cells. When vTR is assembled with hTERT in Unauthenticated Download Date | 5/10/18 10:16 AM CELLULAR & MOLECULAR BIOLOGY LETTERS 599 a cell-free environment, it is able to interact with hTERT and to reconstitute telomerase activity. However, in human cells, vTR does not reconstitute telomerase activity and could not be detected in the human telomerase complex, suggesting that vTR is not able to interact properly with the proteins constituting the human telomerase holoenzyme.

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Marek's disease virus: from miasma to model

Cited by 355 publications

References 118 publications

A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation

A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation

Genomic Variation between Genetic Lines of White Leghorns Differed in Resistance to Marek’s Disease

The human telomerase catalytic subunit and viral telomerase RNA reconstitute a functional telomerase complex in a cell-free system, but not in human cells

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