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糖蛋白L中自然发生的突变对马立克氏病病毒致病机制的影响研究。

Examination of the effect of a naturally occurring mutation in glycoprotein L on Marek's disease virus pathogenesis.

作者信息

Santin Elizabeth R, Shamblin Christine E, Prigge Jonathan T, Arumugaswami Vaithilingaraja, Dienglewicz Robert L, Parcells Mark S

机构信息

Departamento de Medicina Veterinária, Setor de Ciências Agrárias, UFPR, Curitiba-Pr, Brazil.

出版信息

Avian Dis. 2006 Mar;50(1):96-103. doi: 10.1637/7273-090704R1.1.

DOI:10.1637/7273-090704R1.1
PMID:16617990
Abstract

We recently reported a comparison of glycoprotein-encoding genes of different Marek's disease virus pathotypes (MDVs). One mutation found predominantly in very virulent (vv)+MDVs was a 12-bp (four-amino acid) deletion in the glycoprotein L (gL)-encoding gene in four of 23 MDV strains examined (three were vv+MDVs and one was a vvMDV). This mutation was noted in the gL of the TK (615K) strain, but not in the RL (615J) strain of MDV. These strains have identical mutations in the meq gene characteristic of vv+MDVs but can be distinguished by the mutation in the gL-encoding gene. The TK strain was originally isolated from vaccinated chickens and appeared to confer or enhance horizontal transmission of the vaccine virus, herpesvirus of turkeys (HVT). Because the molecular basis for increased virulence of MDV field strains is unknown, we hypothesized that one mechanism might be by coreplication of MDV-1 strains with HVT and that it could be mediated by the mutation of gL, an essential component of the glycoprotein H/L complex. In this study, we compared the pathogenicity of TK (615K) and RL (615J) strains of MDV in the presence and absence of simultaneous HVT coinfection. MDV infections were monitored at the levels of viremia (for both MDV-1 and HVT), clinical signs of MD, tumor incidence, and mortality in 1) inoculated chickens, 2) chickens exposed at 1 day of age, 3) chickens exposed at 2 wk of age, and 4) chickens exposed to both TK/HVT- and RL/HVT-infected chickens at 6 wk of age. We found high incidences of clinical MD signs in all inoculated treatment groups and all chickens exposed to TK and RL viruses, regardless of the presence of HVT. The median time to death of chickens exposed to TK1HVT-infected chickens, however, was lower than the other treatment groups for contact-exposed chickens. Although this difference was not considered to be statistically significant to a rigorously interpreted degree because of the removal of chickens for sampling from the test groups, these data suggest that replication of the TK strain and HVT, when coadministered, might incrementally affect the virulence of MDV-1 strains. The strict correlation of this enhancement of virulence with the mutation in gL, however, requires additional experiments with genetically identical MDV background strains.

摘要

我们最近报道了不同马立克氏病病毒致病型(MDV)糖蛋白编码基因的比较。在非常强毒力(vv)+MDV中主要发现的一个突变是,在所检测的23株MDV中,有4株(3株为vv+MDV,1株为vvMDV)的糖蛋白L(gL)编码基因中有一个12碱基对(四个氨基酸)的缺失。在TK(615K)株的gL中发现了这种突变,但在MDV的RL(615J)株中未发现。这些毒株在vv+MDV特有的meq基因中具有相同的突变,但可通过gL编码基因中的突变加以区分。TK株最初是从接种过疫苗的鸡中分离出来的,似乎赋予或增强了疫苗病毒火鸡疱疹病毒(HVT)的水平传播能力。由于MDV野毒株毒力增强的分子基础尚不清楚,我们推测一种机制可能是MDV-1毒株与HVT共同复制,并且可能由糖蛋白H/L复合体的重要组成部分gL的突变介导。在本研究中,我们比较了MDV的TK(615K)和RL(615J)株在有或无同时感染HVT情况下的致病性。在1)接种鸡、2)1日龄暴露鸡、3)2周龄暴露鸡和4)6周龄暴露于TK/HVT和RL/HVT感染鸡的鸡中,监测MDV感染的病毒血症水平(针对MDV-1和HVT两者)、MD的临床症状、肿瘤发生率和死亡率。我们发现在所有接种处理组以及所有暴露于TK和RL病毒的鸡中,无论是否存在HVT,MD临床症状的发生率都很高。然而,暴露于TK1HVT感染鸡的鸡的中位死亡时间低于接触暴露鸡的其他处理组。尽管由于从试验组中取出鸡进行采样,这种差异在严格解释的程度上不被认为具有统计学意义,但这些数据表明,TK株和HVT共同接种时,其复制可能会逐渐影响MDV-1毒株的毒力。然而,这种毒力增强与gL突变的严格相关性需要使用基因相同的MDV背景毒株进行额外实验。

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