Identification of latency-associated transcripts that map antisense to the ICP4 homolog gene of Marek's disease virus

Cantello, John L.; Anderson, Amy; Morgan, Robin

doi:10.1128/jvi.68.10.6280-6290.1994

Cited by 60 publications

(48 citation statements)

References 30 publications

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“…Recently, Gesser et al demonstrated that one can experimentally infect the nodose ganglia following oral infections of mice and that latent infections are readily established there (88,89). In addition, HSV was shown to establish a latent infection in the nodose ganglia and produce gastric ulcers within the stomach in SCID mice (28). These observations shed some light on the etiology of esophageal mucosal disease that is seen in humans with AIDS (316), and it is possible that further studies will demonstrate that HSV plays a role as a direct or underlying factor in other diseases of the gastrointestinal tract.…”

Section: Sites Of Latent Hsv In Humansmentioning

confidence: 99%

Experimental investigation of herpes simplex virus latency

1997

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The clinical manifestations of herpes simplex virus infection generally involve a mild and localized primary infection followed by asymptomatic (latent) infection interrupted sporadically by periods of recrudescence (reactivation) where virus replication and associated cytopathologic findings are manifest at the site of initial infection. During the latent phase of infection, viral genomes, but not infectious virus itself, can be detected in sensory and autonomic neurons. The process of latent infection and reactivation has been subject to continuing investigation in animal models and, more recently, in cultured cells. The initiation and maintenance of latent infection in neurons are apparently passive phenomena in that no virus gene products need be expressed or are required. Despite this, a single latency-associated transcript (LAT) encoded by DNA encompassing about 6% of the viral genome is expressed during latent infection in a minority of neurons containing viral DNA. This transcript is spliced, and the intron derived from this splicing is stably maintained in the nucleus of neurons expressing it. Reactivation, which can be induced by stress and assayed in several animal models, is facilitated by the expression of LAT. Although the mechanism of action of LAT-mediated facilitation of reactivation is not clear, all available evidence argues against its involving the expression of a protein. Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process.

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Section: Sites Of Latent Hsv In Humansmentioning

confidence: 99%

Experimental investigation of herpes simplex virus latency

1997

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“…The ICP4 homolog is among the alphaherpesvirus gene product homologs that have been identified for MDV (1). Recently, we (11), and others (22,23) have identified a group of latencyrelated RNAs which map antisense to the MDV ICP4 gene. The latency-related RNAs reported so far include two small, spliced RNAs termed MDV small RNAs (MSRs) (11).…”

mentioning

confidence: 99%

“…Recently, we (11), and others (22,23) have identified a group of latencyrelated RNAs which map antisense to the MDV ICP4 gene. The latency-related RNAs reported so far include two small, spliced RNAs termed MDV small RNAs (MSRs) (11). The difference between the MSRs is unknown; therefore, in this report, the two MSR species will be discussed together and considered equivalent.…”

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confidence: 99%

Marek's disease virus latency-associated transcripts belong to a family of spliced RNAs that are antisense to the ICP4 homolog gene

Cantello

Parcells

Anderson

et al. 1997

J Virol

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Marek's disease virus (MDV) latency-associated transcripts include at least two MDV small RNAs (MSRs) and a 10-kb RNA which map antisense to the ICP4 homolog gene and are relatively abundant in MDVtransformed lymphoblastoid cells. This report further describes the biological and structural properties of these RNAs. First, these RNAs were detected in primary lymphomas isolated from chickens infected with several oncogenic MDV strains. Second, the MSRs are nonpolyadenylated, whereas, the 10-kb RNA is predominantly polyadenylated. Third, MSRs localize to the nuclei of both lymphoblastoid cells and cytolytically infected chicken embryo fibroblasts. Fourth, the 3-region splice junctions of the MSRs during latent and productive infection were determined by sequencing RNA-PCR products generated with primers that flank the 3 splice region. The MSRs contain at least three introns, the largest of which overlaps the ICP4 putative translational start site. Fifth, the 5 end of the MSRs initiates approximately 5 kb upstream from the main body of the RNA. The extreme 5 exon is approximately 251 nucleotides (nt) long and is joined to the main body of the transcript upon removal of a 4,852-nt intron. Finally, the 10-kb RNA lies entirely within the repeats flanking the unique short region of the genome. We believe that the MSRs and 10-kb RNA belong to a family of spliced RNAs that map antisense to the ICP4 gene and comprise a complex transcriptional unit expressed during MDV-induced T-cell transformation.

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“…In latently infected lymphocytes there are less than five copies of viral DNA, and latency-associated transcripts are present in the form of a group of RNAs which map antisense to the homologue of the herpes simplex virus (HSV) ICP4 gene (Li et al 1994;Cantello et al 1994).…”

Section: (C) Pathogenesismentioning

confidence: 99%

“…An MDV gene homologous to the ICP4 gene of HSV has been mapped to the inverted repeat flanking the unique short region of the MDV genome (figure 3) (Anderson et al 1992). This gene is of interest because transcripts which map antisense to the ICP4 homologue gene are found in lymphoblastoid cell lines and lymphomas and sense transcripts in lytic MDV infections (table 2) (Li et al 1994;Cantello et al 1994). It has been suggested that the antisense transcripts are latency-associated transcripts and therefore involved in the transformation process as latency is a prerequisite for oncogenesis and maintenance of the transformed state.…”

Section: (F ) Infected Cell Protein 4 (Icp4) Genementioning

confidence: 99%

The Leeuwenhoek Lecture, 1997: Marek's disease herpesvirus: oncogenesis and prevention

Pm¹

1997

Phil. Trans. R. Soc. Lond. B

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There are a number of neoplasias for which a herpesvirus is an essential part of the aetiology. Of these, Marek's disease is the most common and provides excellent opportunities for the study of a herpesvirus-induced tumour both experimentally and under natural conditions in the field. Marek's disease is caused by an alpha herpesvirus; it differs from the other oncogenic herpesviruses which are gamma herpesviruses. It is a ubiquitous virus in poultry populations of the world and is highly cell-associated and contagious, yet only a proportion of infected fowl develop tumours. Evidence is presented to suggest that at least one of the reasons for a wide variation in the incidence of the disease is a temporal interplay between virulent viruses and viruses of low or no virulence. The viral genes associated with the oncogenicity of Marek's disease virus (MDV) are discussed and it is concluded that it is likely that several genes are involved. Finally, a brief history of vaccination to control Marek's disease is given and mode of action discussed. It is concluded that the mechanism of protection is mainly through an antiviral cell mediated immune response, resulting in a lowered challenge virus burden. Marek's disease viruses over the past 40 years have been evolving greater oncogenicity, some of which are not adequately controlled by the vaccines that are currently available. It is suggested that for MDV to produce tumours, there is a need for the cytolytic infection phase and that infection must be with an MDV which possesses a functional gC, ICP4 for maintaining latency which allows the expression of at least the 1.8 kb family, pp38, meq, and possibly pp14 genes, for maintaining the tumour state and possibly initiating this state. Intervention in this process reduces the chance of tumour formation and incidence in a population which can occur through natural or man-mediated infection with non-pathogenic MDVs.

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Identification of latency-associated transcripts that map antisense to the ICP4 homolog gene of Marek's disease virus

Cited by 60 publications

References 30 publications

Experimental investigation of herpes simplex virus latency

Experimental investigation of herpes simplex virus latency

Marek's disease virus latency-associated transcripts belong to a family of spliced RNAs that are antisense to the ICP4 homolog gene

The Leeuwenhoek Lecture, 1997: Marek's disease herpesvirus: oncogenesis and prevention

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