Adaptation of canine distemper virus to canine footpad keratinocytes modifies polymerase activity and fusogenicity through amino acid substitutions in the P/V/C and H proteins

Adaptation of canine distemper virus to canine footpad keratinocytes modifies polymerase activity and fusogenicity through amino acid substitutions in the P/V/C and H proteins
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DOI:
10.1016/j.virol.2006.07.054
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发表时间:
2007-03-01
期刊:
影响因子:
3.7
通讯作者:
Wittek, Riccardo
Wittek, Riccardo
中科院分区:
医学3区
文献类型:
--
作者:
Rivals, Jean-Paul;Plattet, Philippe;Wittek, Riccardo

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野生型犬瘟热病毒(CDV)株A75/17在犬足垫角质形成细胞(CFK)培养物中诱导非杀细胞感染,但产生非常少的子代病毒。在CFK中仅三次传代后,病毒产生了100倍以上的后代,并诱导了有限的细胞病变效应。CFK适应病毒的序列分析显示只有三个氨基酸差异,其中一个位于P/V/C、M和H蛋白中。为了评估哪些氨基酸变化是导致感染性病毒产量增加和感染表型改变的原因,我们产生了一系列重组病毒。他们的分析表明,改变的P/V/C蛋白是导致更高水平的病毒子代形成的原因,而H蛋白质尾区的氨基酸变化是致细胞病变性的主要决定因素。(c)2006年爱思唯尔公司All rights reserved.
The wild-type canine distemper virus (CDV) strain A75/17 induces a non-cytocidal infection in cultures of canine footpad keratinocytes (CFKs) but produces very little progeny virus. After only three passages in CFKs, the virus produced 100-fold more progeny and induced a limited cytopathic effect. Sequence analysis of the CFK-adapted virus revealed only three amino acid differences, of which one was located in each the P/V/C, M and H proteins. In order to assess which amino acid changes were responsible for the increase of infectious virus production and altered phenotype of infection, we generated a series of recombinant viruses. Their analysis showed that the altered P/V/C proteins were responsible for the higher levels of virus progeny formation and that the amino acid change in the cytoplasmic tail of the H protein was the major determinant of cytopathogenicity. (c) 2006 Elsevier Inc. All rights reserved.