• Journal of Veterinary Clinics
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• v.18 no.1
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• pp.55-60
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• 2001

Immunohistochemical and Electron Microscopical Studies on the Initial Skin Lesions Induced Experimentally by Very Virulent Strain of Marek\`s Disease Virus in Chickens Marek\`s disease virus (MDV), which is an avian herpesvirus, causes malignant CD3+CD4+CD8-T cell lymphomas at many sites including visceral organs, muscles, peripheral nerves and skin. In the early skin lesions induced by MDV, corelationship between the translational activity of MDV early gene, pp38 and demonstration of MDV particles in the lymphoid cells are not well studied. Therefore, skin biopsies taken at weekly intervals for 2 weeks from the same specific-pathogen free chicknes inoculated with Md/5 MDV were examined immunohistochemically and electron microscopically. In the skin biopsies sampled at 1 week and 2 weeks post inoculation (PI), feather follicle epithelium (FFE) exhibited usually strong positive reaction for pp38, whereas only few lymphoblasts, which were infiltrated around FFE revealed positive reaction. Electron microscopically, small lymphocytes were detectable in the dermis and subcutaneous skin tissues sampled at 1 week PI. The number of small lymphocytes was increased and pleomorphic lymphoblasts, which were medium to large in size were scattered among the small lymphocytes at 2 weeks PI. Some of lymphoblasts revealed degenerative and necrotic changes. FFE contained a lot of MDV particles in the nucleus including mature and immature ones. Infrequently, immature virus particles were observed not only in the degenerative and necrotic lymphoblasts, but also rarely in the health lymphoblasts. From the present results, spontaneous MDV activation including translational activity of MDV pp38 gene and formation of MDV particles was occurred in the lymphoblasts of early MD skin lesions.

• Korean Journal of Poultry Science
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• v.35 no.3
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• pp.225-240
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• 2008

Marek's disease virus(MDV) is a highly cell-associated, lymphotropic $\alpha$-herpesvirus that causes paralysis and neoplastic disease in chickens. The disease has been controlled by vaccination which was provided the first evidence for a malignant cancer being controlled by an antiviral vaccine. Marek's disease pathogenesis is complex, involving cytolytic and latent infection of lymphoid cells and oncogenic transformation of $CD4^+$ T cells in susceptible chickens. MDV targets a number of different cell types during its life cycle. Lymphocytes play an essential role, although within them virus production is restricted and only virion are produced. Innate and adaptive immune responses develop in response to infection, but infection of lymphocytes results in immunosuppressive effects. Hence in MDV-infected birds, MDV makes its host more vulnerable to tumour development as well as to other pathogens. All chickens are susceptible to MDV infection, and vaccination is essential to protect the susceptible host from developing clinical disease. Nevertheless, MDV infects and replicates in vaccinated chickens, with the challenge virus being shed from the feather-follicle epithelium. The outcome of infection with MDV depends on a complex interplay of factors involving the MDV pathotype and the host genotype. Host factors that influence the course of MD are predominantly the responses of the innate and adaptive immune systems, and these are modulated by: age at infection and maturity of the immune system; vaccination status; the sex of the host; and various physiological factors.

• Korean Journal of Poultry Science
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• v.35 no.1
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• pp.39-55
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• 2008

Like the other herpesviruses, the virion of MDV consists of an envelope, which surrounds an amorphous tegument. Within the tegument, and icosahedral capsid encloses a linear double-stranded DNA core. Although the genome structure of MDV indicates that it is an ${\alpha}-herpesvirus$ like herpes simplex and varicella-zoster viruses, biological properties indicate MDV is more akin to the ${\gamma}-herpesvirus$ group, which includes Epstein-Barr and Kaposi's sarcoma herpesviruses. These herpesviruses replicate lytically in lymphocytes, epithelial and fibroblastic cells, and persist in lymphoblastoid cells. MDV has a complex life cycle and uses two means of replication, productive and non-productive, to exist and propagate. The method of reproduction changes according to a defined pattern depending on changes in virus-cell interactions at different stages of the disease, and in different tissues. Productive (lytic) interactions involve active invasion and take-over of the host cell, resulting in the production of infectious progeny virions. However, some herpesviruses, including MDV, can also establish a non-productive (abortive) infection in certain cell types, resulting in production of cell-associated progeny virus. Non-productive interactions represent persistent infection, in which the viral genome is present but gene expression is limited, there is no structural or regulatory gene translation, no replication, no release of progeny virions and no cell death. Reactivation of the virus is rare, and usually the infectious virus can be re-isolated only after cultivation in vitro. MDV establishes latency in lymphoid cells, some of which are subsequently transformed. In this review article, recent knowledges of the pathogenesis mechanisms followed by MDV infection to sensitive cells and chickens are discussed precisely.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.6
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• pp.679-684
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• 1996

This study evaluates the susceptibility of scaleless mutant chickens to very virulent Marek's disease virus (vvMDV) inoculation. One day old chickens were inoculated subcutaneously with Taiwanese isolates of LTB-1 and LTS-1 strains, and standard strain of Md/5. Compared with the non-inoculated group the vvMDV-inoculated chickens showed decreased body weights and atrophy of lymphoid organs before 35 days old. These results indicate that scaleless chickens show the same susceptibility as the wild type chickens to vvMDV infection. Furthermore, the protective effect of herpesvirus of turkey (HVT) vaccination at 1 day old against vvMDV challenge was evaluated. Scaleless mutant chickens of treated groups showed 20-30% early death, and 85.7-100% and 12.5-14.2% had lymphomatous lesions in visceral organs and peripheral nerves, respectively. No significant lesions were observed in non-challenged chickens of the control group. The HVT vaccination did not provide an effective protection against vvMDV infection. It is concluded that scaleless mutant chickens are susceptible to vvMDV infection.

• Korean Journal of Veterinary Research
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• v.41 no.3
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• pp.373-380
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• 2001

Marek's disease virus (MDV) can cause skin lesions including inflammatory to tumorous. The phenotypical changes of lymphocytes infiltrating in the skin lesions induced by MDV were not clear. Therefore, the skin biopsies taken at weekly intervals for 8 weeks from the same specific-pathogen free chickens inoculated with Md/5 MDV were examined to analysis the phenotypical changes of lymphocytes. Histologically skin lesions progressed from initial inflammatory to late tumorous. Sequentially CD4+ T lymphocytes increased gradually in number from initial skin lesions and were major composition cells in the tumor lesions. Regardless of inflammatory or tumor lesions, CD8+ T cells and ${\gamma}{\delta}$ T cells infiltrated particularly in the dermis and subcutaneous on which MDV was actively replicated in the feather follicle epithelium(FFE). In addition, IgG bearing B lymphocytes in considerable number infiltrated in the dermis and subcutaneous tissues. From these results, the development of MDV-induced skin lesions was inflammatory following tumorous. In addition, each CD8+, ${\gamma}{\delta}$ and CD4+ T cells and B cell might act to protect MDV replication in the FFE or tumor cells which turned on lytic cycle.

• Korean Journal of Veterinary Research
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• v.38 no.1
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• pp.101-106
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• 1998

The present study attempted to apply polymerase chain reaction (PCR) to develop a rapid differential diagnosis among Marek's disease, reticuloendotheliosis and avian leukosis. The primers chosen to detect Marek's disease virus (MDV) flank the 132bp tandem direct repeat of the MDV genome. The primers selected for reticuloendotheliosis virus (REV) and avian leukosis virus (ALV) are based on proviral long terminal repeats of spleen necrosis virus and Rous-associated virus-2 genomes, respectively. The specific PCR products of MDV, REV and ALV were observed with each primer and the reaction was not cross-reacted among the viruses. MDV-specific DNA was also amplified from the MDV-induced lymphoma (MDCC-MSB1) but not from the REV-induced tumor and ALV-induced lymphoma (LSCC-1104B1). In addition, proviral DNA of REV from REV-induced tumor and proviral DNA of ALV from ALV-induced lymphoma were also amplified by REV-specific and ALV-specific PCRs, respectively. Therefore these three PCR methods may be used to rapidly differentiate among MDV, REV and ALV-associated tumors in diagnosis.

• Korean Journal of Veterinary Pathology
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• v.6 no.2
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• pp.101-104
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• 2002

닭의 전신장기에 림프종 발생이 특정인 마렉병(Marek's disease; MD)은 림프구성 백혈병(Lymphoid leukosis; LL)과 병리학적 소견이 매우 유사하여 감별이 요구된다. 마렉병 바이러스(Marek's disease virus; MDV)는 질병초기에서 후기에 이르기까지 모낭상피세포에 세포용해성 감염을 지속적으로 일으킨다. 세포용해성 감염이 있는 모낭상피세포는 변성내지 괴사되어 있고 핵내봉입체가 관찰된다. 또한 세포용해성 감염이 있는 모낭상피세포 바로 밑의 진피와 깃털 수질(feather pulp)내의 혈관주위에 림프구 침윤이 관찰된다. 이러한 피부병변은 MD의 특징적인 병변들로서 LL과 감별할 수 있는 결정적인 단서이다. 본 고에서는 MD에 관한 전반적인 것과 특히 MD 진단을 위한 피부병변의 유용성에 대해서 자세히 논하고자 한다. 양계산업에 문제를 야기하고 있는 림프구 증식성 종양은 크게 마렉병(Marek’s disease; MD)과 백혈병(Lymphoid leukosis; LL)이 있다. 이들 질환의 원인체들이 분리되기 전까지는 이들 질병들은 발병부위에 따라 질병명을 붙였다. 즉, 내부장기냐 근육에 발생한 것은 visceral lymphomatosis, 피부에 발생한 것은 skin leukosis, 말초신경의 병변은 poly­n neuritis, neuritis, neurolymphomatosis gallinarum, range paralyis로 불리었다. 또한 눈에 발생한 것은 blindness, gray eye, iritis, uveitis, ocular lymphomatosis라고 불리었다. 1961년에 Biggs는 이러한 림프구 증식성 질병을 마렉병과 백혈병 으로 분류하자는 제안을 하였고, 드디어 1960년대 중반에 림프구 증식성 병변 중의 일부에서 herpesvirus가 분리되어서 Biggs가 제안한 병명인 마렉병을 본격적으로 사용하게 되었다. MD는 마렉병 바이러스(Marek’s disease virus; MDV)가 원 인제로서 닭에 전염성이 강한 염증성에서 종양성의 병변을 내부장기, 피부, 근육, 안구, 중추신경계, 말초신경계 등에 일 으킨다. MDV는 림프종을 유발하기 때문에 처음에는 사람에서 림프종을 유발하는 Epstein-Bar 바이러스와 관련이 있을 것으로 생각되어 gamma-herpesvirus로 분류되었지만, MDV의 게놈 구조와 세포배양에서 빠르게 성장한다는 점 때문에 지금은 alpha-herpesvirus로 재분류 되었다. MDV는 바이러스 중화시험과 한천 겔 침강법에 의해서 3개의 혈청형으로 분류 된다. 혈청형 1은 종양원성 바이러스와 종양원성 바이러스의 계대배양에 의한 약독주가 있다. 혈청형 2는 자연적으로 발 생하는 비종양원성 닭의 MDV이고, 혈정형 3은 바종양원성 칠면조 herpesvirus (HVT)이다. 림프종을 유발하는 MDV 감염은 4개의 과정, 즉 초기 세포용해성 감염, 잠복감염, 후기 세포용해성 감염, 마지막으로 종양화로 나눌 수 있다. 감염의 경로를 보면, 흡입된 MDV는 폐의 대식세포에 감염한 후 전선 장기로 MDV를 전파 시킨다. 특히, 흉선, F냥, 비장 등의 림프구에 초기 세포용해성 감염을 일으키는데, B 림프구가 주로 감염된다. 세포용해성 감염음 방어하기 위해 몰려든 T 림프구가 활성화가 되면, T 세포도 감염되게 된다. 잠복감염은 여러 가지 사이토카인 등 을 포함한 면역반응에 의해서 일어나며, 이 때 잠복감염된 세포는 특히 혈중의 T 세포라고 한다. 혈중 MDV 감염세포 는 피부 모낭상피세포, 선장 등 상피세포 유래의 조직에 MDV를 전파 시켜서 이들 조직에서 후기 세포용해성 감염이 일어나게 한다. 후기 세포용해성 감염을 유발하는 것은 이러한 MDV가 감염된 혈중 림프구라는 증거는 혈중의 세포 외에는 감염성 바이러스가 없기 때문이다. 후기 세포용해성 감염이 있는 후 육안적 혹은 현미경적으로 검출이 가능한 림프종이 여러 장기에서 관찰된다. MDV가 감염되면 병변 발생부위에 따라서 다양한 임상증상이 발생한다. 즉 내부장기에 병변이 있을 경우는 침울, 체중감소, 산란율 저하 등이 발생하며, 신경계는 발생부위별 신경증상이 일어난다. 이러한 장기나 조직에서는 육안적으로 백색에서 회백색의 종양성 병변이 관찰된다. 말초신경에 병변이 발생한 경우에는 특히 좌골신경 및 신경총에서 호발하는데, 이들 조직은 편측성 혹은 양측성으로 종창되어 있다. 안구는 간혹 육안적으로 식별이 가능한 홍채 퇴색 및 증식 병변이 관찰된다. 피부형 MD는 특히 육용계에서 문제가 되고 있으며, 산란계의 내장형 MD가 발생한 경우에도 피부를 자세히 설펴보면 피부형 MD를 간혹 관찰할 수 있다. 피부형 MD는 모낭주위에 원형의 결절형태로 발생하는데, 이들 병변이 커지면 바로 옆의 병변과 융합 되어 큰 결절을 형성하기도 한다. (중략)

• Journal of Korea Water Resources Association
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• v.53 no.11
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• pp.929-938
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• 2020

In this study, we estimated missing evapotranspiration (ET) data at a eddy-covariance flux tower in the Cheongmicheon farmland site using the Artificial Neural Network (ANN). The ANN showed excellent performance in numerical analysis and is expanding in various fields. To evaluate the performance the ANN-based gap-filling, ET was calculated using the existing gap-filling methods of Mean Diagnostic Variation (MDV) and Food and Aggregation Organization Penman-Monteith (FAO-PM). Then ET was evaluated by time series method and statistical analysis (coefficient of determination, index of agreement (IOA), root mean squared error (RMSE) and mean absolute error (MAE). For the validation of each gap-filling model, we used 30 minutes of data in 2015. Of the 121 missing values, the ANN method showed the best performance by supplementing 70, 53 and 84 missing values, respectively, in the order of MDV, FAO-PM, and ANN methods. Analysis of the coefficient of determination (MDV, FAO-PM, and ANN methods followed by 0.673, 0.784, and 0.841, respectively.) and the IOA (The MDV, FAO-PM, and ANN methods followed by 0.899, 0.890, and 0.951 respectively.) indicated that, all three methods were highly correlated and considered to be fully utilized, and among them, ANN models showed the highest performance and suitability. Based on this study, it could be used more appropriately in the study of gap-filling method of flux tower data using machine learning method.

• Korean Journal of Veterinary Pathology
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• v.5 no.2
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• pp.49-56
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• 2001

Ocular lesions induced in 40 specific-pathogen-free Marek's disease (MD) resistant chicks by inoculation at 1 day of age with very virulent strain of Marek's disease virus (WV) were pathologically examined. Grossly,24/40 (60%) chicks had white gel-like materials in the vitreous body, whereas thickening and discoloration of iris (gray eye) were not observed. Microscopically, characteristic ocular MD lesions were observed in choroid (27/40), ciliary (30/40) and iris (23/40) in which small focal inflammatory to diffuse neoplastic Iymphoid cells were infiltrated. Five out of 40 MDV-inoculated birds revealed necrotizing Iymphomas in choroid. These lesions consisted of necrotic and degenerating Iymphoblasts accompanied by intranuclear inclusion body. There was retinal atrophy and necrosis with inclusion body detected in necrotic ganglion, inner or outer nuclear and infiltrated Iymphoblast cells. Conjunctiva showed lymphoid cell infiltration in 29/40 chicks inoculated with MDV, Vitreous body exhibited mild to severe exudation of eosinophilic proteinaceous material in 24/40 chicks. These lesions were associated with Iymphoid cell infutration, edema and fibrosis of choroid. Pecten (7/40) and optic nerve (13/40) were infiltrated usually mildly with Iymphoid cells. From these results, very virulent strain, Md/5 of MDV caused high incidence of ocular lesions in MD resistant chicks. In addition, Md/5 induced exudation of proteinaceous material into the vitreous body and fibrosis of choroid. Necrotizing ocular Iymphoma lesions in choroid is the first report in the MD literature.

• Korean Journal of Poultry Science
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• v.34 no.1
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• pp.57-76
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• 2007

Marek's disease (MD) is caused by a ubiquitous, lymphotropic alphaherpesvirus, MD virus (MDV). MD has been a major concern in the poultry industry due to the emergence of increasingly virulent strains over the last few decades that were isolated in the face of comprehensive vaccination. MD is characterized by a variety of clinical signs, amongst them neurological symptoms, chronic wasting, and most notably the development of multiple lymphomas that manifest as solid tumors in the viscera and musculature. Much work has been devoted to study MD-induced oncogenesis and genes involved in this process. Among the many genes encoded by MDV, a number have recently been shown to affect the development of tumors in chickens, one protein directly causing transformation of cells (Meq) and another being involved in maintaining transformed cells (vTR). Other MDV gene products modulate and are involved in early lytic in vivo replication, thereby increasing the chance of transformation occurring. In this review, specific genes encoded by MDV that are involved in the initiation and/or maintenance of transformation were briefly summarized, and limits of current vaccination and new control strategies against MD, particularly how modem molecular biological methods may be used to improve strategies to combat the disease in the future, were discussed.