A mutant of herpes simplex virus type 1 in which the UL13 protein kinase gene is disrupted

Coulter, Lesley J.; Moss, H; Lang, Jas C.; McGeoch, Duncan J.

doi:10.1099/0022-1317-74-3-387

Cited by 112 publications

(118 citation statements)

References 18 publications

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“…This was in agreement with the results obtained for other alphaherpesviruses. Indeed, the UL13 ortholog was found to be non essential for the replication of PRV, HSV-1, and VZV in cultured cells [5,9,15]. In this study, we also report that no difference can be observed between rRB-1B and rRB-1B*UL13 with respect to plaque size.…”

Section: Discussionsupporting

confidence: 57%

“…The biological functions of pUL13 are still unclear. Studies on mutant viruses indicate that UL13 is dispensable for replication in cell culture [5]. The suppression of the UL13 kinase activity is associated to the formation of smaller plaques [30].…”

Section: Introductionmentioning

confidence: 99%

“…It can phosphorylate itself and at least five other viral proteins: VP22, ICP22, ICP0, the unique-short protein kinase pUS3, and gE [5,6,12,19,20,22]. pUL13 can also phosphorylate cellular factors such as the eukaryotic elongation factor ∂EF-1 [13].…”

Section: Introductionmentioning

confidence: 99%

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A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for tumor formation and feather follicle tropism and cannot restore horizontal virus transmission of rRB-1B in vivo

et al. 2007

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-Marek's disease virus (MDV) is an oncogenic alphaherpesvirus that is highly contagious in poultry. Recombinant RB-1B (rRB-1B) reconstituted from an infectious genome cloned as a bacterial artificial chromosome (BAC) is unable to spread horizontally, quite in contrast to parental RB-1B. This finding suggests the presence of one or several mutations in cloned relative to parental viral DNA. Sequence analyses of the pRB-1B bacmid identified a one-nucleotide insertion in the UL13 orthologous gene that causes a frame-shift mutation and thereby results in a theoretical truncated UL13 protein (176 aa vs. 513 aa in parental RB-1B). UL13 genes are conserved among alphaherpesviruses and encode protein kinases. Using two-step "en passant" mutagenesis, we restored the UL13 ORF in pRB-1B. After transfection of UL13-positive pRB-1B DNA (pRB-1B*UL13), the resulting, repaired virus did not exhibit a difference in cell-to cell spread (measured by plaque sizes) and in UL13 transcripts in culture compared to parental rRB-1B virus. Although 89% of the chickens inoculated with rRB-1B*UL13 virus developed tumors in visceral organs, none of the contact birds did. MDV antigens were clearly expressed in the feather tips of rRB-1B infected chickens, suggesting that the UL13 gene mutation did not alter virus tropism of the feather follicle. The results indicate that the correction in UL13 gene alone is not sufficient to restore in vivo spreading capabilities of the rRB-1B virus, and that other region(s) of pRB-1B might be involved in the loss-of-function phenotype. This finding also shows for the first time that a full UL13 ORF is dispensable for MDV tumor formation and feather follicle tropism.Marek's disease virus / UL13 / pathogenesis / horizontal spread / chicken

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Section: Discussionsupporting

confidence: 57%

Section: Introductionmentioning

confidence: 99%

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A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for tumor formation and feather follicle tropism and cannot restore horizontal virus transmission of rRB-1B in vivo

et al. 2007

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“…Structural analysis of purified virions of several herpesviruses, including HSV, CMV, and EBV, indicate that these protein kinases are asso-ciated with virus particles (2,12,37,50,52); thus, the kinases are in a position to influence virion assembly and events that take place after entry of the virion into the cell. A number of studies using kinase-null viral mutants demonstrated the importance of the kinase for regulating viral gene expression, replication, tissue tropism, or infection in animal models (7,11,26,35,41,48). Various studies have implicated the viral protein kinase in influencing viral gene expression (6,58), viral DNA replication (27,52,53), or nucleocapsid egress from the nucleus during virus assembly (26,34,53).…”

mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus-Encoded Protein Kinase and Its Interaction with K-bZIP

Izumiya

Geelen

et al. 2007

J Virol

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The oncogenic herpesvirus, Kaposi's sarcoma-associated herpesvirus, also identified as human herpesvirus 8, contains genes producing proteins that control transcription and influence cell signaling. Open reading frame 36 (ORF36) of this virus encodes a serine/threonine protein kinase, which is designated the viral protein kinase (vPK). Our recent efforts to elucidate the role of vPK in the viral life cycle have focused on identifying viral protein substrates and determining the effects of vPK-mediated phosphorylation on specific steps in viral replication. The vPK gene was transcribed into 4.2-kb and 3.6-kb mRNAs during the early and late phases of viral reactivation. vPK is colocalized with viral DNA replication/transcription compartments as marked by a polymerase processivity factor, and K-bZIP, a protein known to bind the viral DNA replication origin (Ori-Lyt) and to regulate viral transcription. The vPK physically associated with and strongly phosphorylated K-bZIP at threonine 111, a site also recognized by the cyclin-dependent kinase Cdk2. Both K-bZIP and vPK were corecruited to viral promoters targeted by K-bZIP as well as to the Ori-Lyt region. Phosphorylation of K-bZIP by vPK had a negative impact on K-bZIP transcription repression activity. The extent of posttranslational modification of K-bZIP by sumoylation, a process that influences its repression function, was decreased by vPK phosphorylation at threonine 111. Our data thus identify a new role of vPK as a modulator of viral transcription.Kaposi's sarcoma-associated herpesvirus (KSHV), also designated human herpesvirus 8, has been linked to several malignancies, including Kaposi's sarcoma, B-cell lymphomas, primary effusion lymphomas, and multicentric Castleman's disease in immunocompromised individuals (reviewed in reference 46). Kaposi's sarcoma is the most common malignancy associated with AIDS (45). The viral genome is doublestranded DNA, approximately 165 kbp, and encodes over 81 open reading frames (ORFs) (43). The majority of the ORFs are essential for viral replication and include genes necessary for viral DNA replication, transcription, and assembly of infectious particles (51). In addition, the KSHV genome contains a large number of ORFs with homology to known cellular genes. Several of these viral ORFs are implicated in modulating host immune responses, promoting angiogenesis, and dysregulating cell growth (14). A model for regulated expression of KSHV genes has been deduced from numerous genetic and biochemical studies of viral RNA patterns and activities of viral transactivators (22,31,39,49). As for other herpesviruses, KSHV genes in productive infection have been classified into the following temporally distinct classes: immediate-early, early, and late. This virus can also establish a latent state that is characterized by presence of a multicopy circular episome of viral DNA, which expresses a small subset of viral proteins. Productive (lytic) viral replication can be induced by treatment of latently infected cell lines with butyrate,...

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“…To date, the only HSV-1 tegument protein shown to be essential for virus assembly is VP16, which is encoded by gene UL48 (Ace et al, 1988 ;Weinheimer et al, 1992). Studies on deletion mutants have revealed that in the absence of other tegument components, including the abundant species VP11\12 and VP13\14, virus assembly can continue and viable virus is produced (Fenwick & Everett, 1990 ;Coulter et al, 1993 ;Zhang & McKnight, 1993). Thus, the tegument would appear to be capable of accommodating significant changes in composition without disabling virus production.…”

mentioning

confidence: 99%

The abundance of the herpes simplex virus type 1 UL37 tegument protein in virus particles is closely controlled.

McLauchlan¹

1997

Journal of General Virology

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The tegument region of herpes simplex virus type 1 virus particles contains approximately 15 virusencoded polypeptide species. One of the less abundant species is a 120 kDa protein specified by gene UL37. The abundance of the UL37 protein in infected cells was increased about 20-fold by replacing the native promoter for gene UL37 with the strong immediate early promoter of human cytomegalovirus. This rise in abundance did not induce any detectable increase in the amount of UL37 protein incorporated into virus particles. These data contrast with those previously obtained for a second tegument protein VP22 whose level of incorporation was elevated by increasing its abundance in infected cells. Thus, for the UL37 protein, a mechanism exists to control its abundance in the tegument. Moreover, data obtained with light particles which lack the viral capsid suggest that this controlled incorporation is not directed by interaction with the capsid structure.

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A mutant of herpes simplex virus type 1 in which the UL13 protein kinase gene is disrupted

Cited by 112 publications

References 18 publications

A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for tumor formation and feather follicle tropism and cannot restore horizontal virus transmission of rRB-1B in vivo

A full UL13 open reading frame in Marek's disease virus (MDV) is dispensable for tumor formation and feather follicle tropism and cannot restore horizontal virus transmission of rRB-1B in vivo

Kaposi's Sarcoma-Associated Herpesvirus-Encoded Protein Kinase and Its Interaction with K-bZIP

The abundance of the herpes simplex virus type 1 UL37 tegument protein in virus particles is closely controlled.

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