Arumugaswami Vaithilingaraja, Kumar Pankaj M, Konjufca Vjollca, Dienglewicz Robert L, Reddy Sanjay M, Parcells Mark S
Center of Excellence for Poultry Science, University of Arkansas, Fayetteville, AR 72701, USA.
Avian Dis. 2009 Jun;53(2):156-65. doi: 10.1637/8384-062308-Reg.1.
Marek's disease virus (MDV) is an alphaherpesvirus of chickens that causes the paralysis and rapid lymphoma formation known as Marek's disease. MDV establishes latent infection in activated CD4+ T-cells, and these cells are also the target for transformation. MDV latency has been studied using MDV lymphoma-derived cell lines and T-cells isolated from infected chickens. Each of these models has limitations because MDV-transformed cell lines require the use of oncogenic viruses; conversely, pools of latently infected cells are in relatively low abundance and invariably contain cells undergoing reactivation to lytic infection. In this study we have examined the spontaneous and induced expression of the MDV genome, the effect of genome uptake on cellular proliferation and apoptosis resistance, and differences in cellular surface antigen expression associated with MDV genome uptake in a reticuloendotheliosis virus (REV)-transformed T-cell model. We report that the MDV genome is highly transcribed during this latent infection, and that the expression of Marek's EcoRI-Q-encoded protein (Meq) transcripts is similar to that of MDV-transformed cells, but is somewhat lower than MDV-transformed cells at the protein level. Uptake of the MDV genome was associated with an increased growth rate and resistance to serum starvation-induced apoptosis. Treatment of cells with bromodeoxyuridine induced the expression of MDV lyric antigens in a manner similar to MDV-transformed cells. Uptake of the MDV genome, however, was not consistently associated with alteration ofT-cell surface antigen expression. Overall, our data show that the REV-transformed cell line model for MDV latency mimics many important aspects of latency also observed in MDV-transformed cells and provides an additional tool for examining MDV latent infection.
马立克氏病病毒(MDV)是鸡的一种α疱疹病毒,可引发称为马立克氏病的麻痹和快速淋巴瘤形成。MDV在活化的CD4 + T细胞中建立潜伏感染,而这些细胞也是转化的靶标。已使用源自MDV淋巴瘤的细胞系和从受感染鸡中分离的T细胞研究了MDV潜伏期。这些模型中的每一个都有局限性,因为MDV转化的细胞系需要使用致癌病毒;相反,潜伏感染细胞池的丰度相对较低,并且总是包含正在经历向裂解感染再激活的细胞。在本研究中,我们在网状内皮组织增生症病毒(REV)转化的T细胞模型中,研究了MDV基因组的自发和诱导表达、基因组摄取对细胞增殖和抗凋亡的影响,以及与MDV基因组摄取相关的细胞表面抗原表达差异。我们报告说,在这种潜伏感染期间MDV基因组被高度转录,并且马立克氏EcoRI-Q编码蛋白(Meq)转录本的表达与MDV转化细胞的表达相似,但在蛋白质水平上略低于MDV转化细胞。MDV基因组的摄取与生长速率增加和对血清饥饿诱导的凋亡的抗性相关。用溴脱氧尿苷处理细胞以类似于MDV转化细胞的方式诱导MDV裂解抗原的表达。然而,MDV基因组的摄取与T细胞表面抗原表达的改变并不一致相关。总体而言,我们的数据表明,用于MDV潜伏期的REV转化细胞系模型模拟了在MDV转化细胞中也观察到的潜伏期的许多重要方面,并为检查MDV潜伏感染提供了额外的工具。