Differential attenuation of the induction by Marek's disease virus of transient paralysis and persistent neurological disease: A model for pathogenesis studies

Gimeno, Isabel M.; Witter, R. L.; Hunt, Henry D.; Reddy, Sanjay M.; Neumann, Ulrich

doi:10.1080/03079450120066403

Cited by 29 publications

(10 citation statements)

References 38 publications

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“…Forms of MD include acute neoplastic disease with lymphomatous lesions in several organs, severe cytolytic forms with extensive lymphoid atrophy, and an acute form of transient paralysis (Gimeno et al, 2001). The immediate nature of the onset of MD lymphomas, sometimes as early as within a few weeks after infection, indicate rapid activation of genes associated with oncogenicity, possibly through virus-induced genes.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

Lambeth

Yao

Smith

et al. 2009

Journal of General Virology

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MicroRNAs (miRNAs) are a class of short RNAs that function as post-transcriptional suppressors of protein expression and are involved in a variety of biological processes, including oncogenesis. Several recent studies have implicated the involvement of miR-221 and miR-222 in tumorigenesis as these miRNAs are upregulated in a number of cancers and affect the expression of cell cycle regulatory proteins such as the cyclin-dependent kinase (cdk) inhibitor p27Kip1. Marek's disease virus (MDV) is a highly oncogenic herpesvirus that affects poultry, causing acute neoplastic disease with lymphomatous lesions in several organs. MDV-encoded oncogenes such as Meq are directly implicated in the neoplastic transformation of T cells and have been well studied. More recently, however, the involvement of both host and virus-encoded miRNAs in the induction of MD lymphomas is being increasingly recognized. We analysed the miRNA expression profiles in the MDV-transformed lymphoblastoid cell line MSB-1 and found that endogenous miRNAs miR-221 and miR-222 were significantly upregulated. Demonstration of the conserved binding sites for these miRNAs in the chicken p27Kip1 3′-untranslated region sequence and the repression of luciferase activity of reporter constructs indicated that miR-221 and miR-222 target p27Kip1 in these cells. We also found that overexpression of miR-221 and miR-222 decreased p27Kip1 levels and that treatment with retrovirally expressed antagomiRs partially alleviated this suppression. These data show that an oncogenic herpesvirus, as in the case of many cancers, can exploit the miRNA machinery for suppressing cell cycle regulatory molecules such as p27Kip1 in the induction and progression of T-cell lymphomas.

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Section: Introductionmentioning

confidence: 99%

MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

Lambeth

Yao

Smith

et al. 2009

Journal of General Virology

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“…Although highly virulent MDV strains are reported to induce acute neuropathology, even during the first phase of MDV infection (Cho et al, 1998;Witter et al, 1999;Gimeno et al, 2001), only chickens which ultimately exhibit MD-related progressive pathology progress to stage (3) and beyond. Because all the chickens in a flock are not equally susceptible to MD, the pathogenesis of MDV infection may vary between individual flockmates.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Marek's disease virus load in peripheral blood lymphocytes at various stages of infection and clinical Marek's disease in broiler chickens

Walkden‐Brown

Islam

Underwood³

et al. 2006

Avian Pathology

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Vaccination with herpesvirus of turkey (HVT) vaccine provides protection against clinical Marek's disease (MD) but does not preclude infection with wild-type MD virus (MDV). The quantity of MDV detected in circulating lymphocytes during the early period after infection may be a useful predictor of subsequent clinical MD later in the life. A study was designed to quantify MDV and HVT copy number in peripheral blood lymphocytes (PBL) using real-time polymerase chain reaction between days 5 and 35 post-challenge and to relate this to subsequent development of gross MD lesions. Female commercial broiler chickens were vaccinated with HVT or were sham-vaccinated at hatch, then challenged with MDV strain MPF-57 at day 2 post-vaccination and reared in positive-pressure isolators up to 56 days post-challenge, when all survivors were euthanized. All dead and euthanized chickens were examined post mortem for gross MD lesions. Birds were scored for MD lesions and mortality. MDV and HVT genome copy numbers were determined for each PBL sample. There was an increase in HVT load in PBL between days 7 and 37 post-vaccination, with marked increases between days 7 and 16 and again between days 30 and 37. There was a steady increase in MDV load to 35 days post-challenge. The mean MDV copy number (log 10 ) was greater in chickens subsequently exhibiting gross MD lesions (5.059/0.21) than in those that did not (2.889/0.223), with the largest difference at 14 and 21 days post-challenge (P B/0.001). Quantification of MDV during early infection is therefore a potential tool for monitoring MD in broiler flocks.

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“…Replication of RM1 strain had unique features. The replication of RM1 strain differed not only from CVI988 and 648A80 but also from what has been described for other attenuated strains or even oncogenic strains (Schat et al, 1985;Gimeno et al, 2001;Reddy et al, 2002). The RM1 strain seemed to have a particular tropism for thymus.…”

Section: Discussionmentioning

confidence: 60%

“…MD vaccines attenuated in cell culture do not induce lymphoid organ atrophy (Schat et al, 1985;Gimeno et al, 2001). However, MDV strains attenuated by the insertion of REV LTR Kim et al, 2011) and those attenuated by deletion of the oncogene meq induce severe atrophy in the lymphoid organs when inoculated in chickens lacking maternal antibodies against MDV (Lupiani et al, 2004;Lee et al, 2010;).…”

Section: Introductionmentioning

confidence: 95%

“…Infection of lymphocytes in vitro is impaired after MDV attenuation in cell culture and this might contribute to the decreased in vivo replication (Schat et al, 1985). Most attenuated serotype 1 MDV strains do not induce an early cytolytic infection in the lymphoid organs (Schat et al, 1985;Gimeno et al, 2001). Attenuated serotype 1 MDV strains can be isolated from blood and spleen by the traditional plaque assay and can be detected in blood, spleen, and feather pulp by real-time polymerase chain reaction (PCR) (Schat et al, 1985;Witter et al, 1995;Gimeno et al, 2004;Baigent et al, 2007;Dudnikova et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection

Gimeno

Witter²,

Cortes

et al. 2011

Avian Pathology

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The present work is a chronological study of the pathogenesis of three attenuated serotype 1 Marek's disease (MD) virus strains (RM1, CVI988 and 648A80) that provide high protection against MD but have been attenuated by different procedures and induce different degrees of lymphoid organ atrophy. All studied strains replicated in the lymphoid organs (bursa,x thymus and spleen) and a peak of replication was detected at 6 days post inoculation (d.p.i.). Differences, however, were observed among vaccine strains. RM1 strain replicates more in all lymphoid organs compared with CVI988 and 648A80 strains. In addition, replication of RM1 in the thymus did not decrease after 6 d.p.i. but continued at high levels at 14 d.p.i. and until the thymus was completely destroyed. Lung infection occurred very early after infection with all of the three vaccines and the level of replication was similar to that found in the lymphoid organs. Infected cells were very large and appeared scattered in the lung parenchyma and in the parabronchial lining. The study of the target cells for the early infection in cell suspensions of blood and spleen showed that both non-adherent cell populations (enriched in lymphoid cells) and adherent cells (enriched in monocytes/macrophages) supported MD virus infection. Infection in adherent cells was especially high at very early stages of the infection (3 to 6 d.p.i.). Atrophy of lymphoid organs is a major drawback in the production of highly protective vaccines against MD. A better understanding of the mechanisms associated with lymphoid organ atrophy will aid in overcoming this problem.

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Differential attenuation of the induction by Marek's disease virus of transient paralysis and persistent neurological disease: A model for pathogenesis studies

Cited by 29 publications

References 38 publications

MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

MicroRNAs 221 and 222 target p27Kip1 in Marek's disease virus-transformed tumour cell line MSB-1

Relationship between Marek's disease virus load in peripheral blood lymphocytes at various stages of infection and clinical Marek's disease in broiler chickens

Replication ability of three highly protective Marek's disease vaccines: implications in lymphoid organ atrophy and protection

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