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12株火鸡出血性肠炎病毒分离株的比较有助于预测影响毒力的遗传因素。

Comparison of 12 turkey hemorrhagic enteritis virus isolates allows prediction of genetic factors affecting virulence.

作者信息

Beach Nathan M, Duncan Robert B, Larsen Calvert T, Meng Xiang-Jin, Sriranganathan Nammalwar, Pierson F William

机构信息

Center for Molecular Medicine and Infectious Disease, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, 1410 Price's Fork Road, Blacksburg, VA 24061, USA.

出版信息

J Gen Virol. 2009 Aug;90(Pt 8):1978-1985. doi: 10.1099/vir.0.010090-0. Epub 2009 Apr 22.

Abstract

Turkey hemorrhagic enteritis virus (THEV) is a member of the genus Siadenovirus and causes disease in turkey poults characterized by splenomegaly, bloody diarrhoea and death. The mechanism responsible for intestinal lesion formation and mortality is not known, although there is strong evidence that it is immune-mediated. All strains of THEV are serologically indistinguishable, although there are naturally occurring avirulent strains of THEV that replicate efficiently in turkeys without the intestinal haemorrhage or mortality associated with more virulent strains. The purpose of this study was to determine which viral genes are involved in virulence. The full-length genome of an avirulent vaccine strain was sequenced and compared with the genome of a virulent field isolate from Israel that was sequenced in 1998. Comparison of the two 26.3 kb genomes revealed 49 nucleotide differences resulting in 14 putative amino acid changes within viral proteins. Sequencing of the regions surrounding the 14 missense mutations revealed variations in ORF1, E3 and the fiber (fib) knob domain in five additional strains with varying degrees of virulence. Complete sequences of these genes were determined in a total of 11 different strains of THEV. All strains had at least one missense mutation in ORF1, and all but two of the strains had one missense mutation in E3. At least one missense mutation was found in the fiber knob domain in six out of seven virulent strains. Sequence variation of ORF1, E3 and fib in strains of THEV with different phenotypes strongly indicates that these genes are the key factors affecting virulence.

摘要

火鸡出血性肠炎病毒(THEV)是唾液腺病毒属的成员,可导致幼火鸡发病,其特征为脾肿大、血性腹泻和死亡。尽管有强有力的证据表明肠道病变形成和死亡是由免疫介导的,但导致这些病变的机制尚不清楚。所有THEV毒株在血清学上无法区分,不过存在自然发生的无毒力毒株,它们能在火鸡中高效复制,且不会出现与更具毒力毒株相关的肠道出血或死亡现象。本研究的目的是确定哪些病毒基因与毒力有关。对一株无毒力疫苗毒株的全长基因组进行了测序,并与1998年测序的一株来自以色列的有毒力田间分离株的基因组进行了比较。对这两个26.3 kb基因组的比较揭示了49个核苷酸差异,导致病毒蛋白内有14个推定的氨基酸变化。对14个错义突变周围区域的测序显示,在另外5株具有不同程度毒力的毒株中,ORF1、E3和纤维(fib)柄结构域存在变异。在总共11株不同的THEV毒株中确定了这些基因的完整序列。所有毒株在ORF1中至少有一个错义突变,除两株外,所有毒株在E3中都有一个错义突变。在7株有毒力的毒株中,有6株在纤维柄结构域中至少发现了一个错义突变。不同表型的THEV毒株中ORF1、E3和fib的序列变异强烈表明这些基因是影响毒力的关键因素。

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