Molecular determinants of disease in coxsackievirus B1 murine infection.

Molecular determinants of disease in coxsackievirus B1 murine infection.
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DOI:
10.1002/jmv.22133
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发表时间:
2011-09
影响因子:
12.7
通讯作者:
Gomez, Ricardo M.
Gomez, Ricardo M.
中科院分区:
医学3区
文献类型:
--
作者:
Cifuente, Javier O.;Ferrer, Maria F.;Jaquenod de Giusti, Carolina;Song, Wen-Chao;Romanowski, Victor;Hafenstein, Susan L.;Gomez, Ricardo M.

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为了更好地了解不同基因组区域如何赋予柯萨奇病毒 B (CVB) 致病性,研究了两种型内 CVB1 变体和多种重组病毒。测序分析显示亲本非致病性CVB1N和致病性CVB1Nm之间有23个核苷酸变化。与其他 CVB 序列相比,CVB1Nm 中存在的突变比 CVB1N 中的突变更为保守。 C3H/HeJ 小鼠接种表明 P1 区域对于小鼠胰腺和心脏的致病性至关重要。这些器官疾病的分子决定因素部分重叠。几个 P1 区氨基酸差异似乎位于衰变加速因子 (DAF) 足迹 CVB 中。 CVB1N 和 CVB1Nm 与人 CAR 相互作用,但只有 CVB1N 似乎与人 DAF 相互作用,这是在空斑减少测定中使用可溶性受体确定的。然而,鼠同源物 Daf-1 不与任何通过血凝评估的病毒相互作用。这项研究的结果表明,未知受体与病毒的相互作用在 CVB1Nm 的致病性中发挥着重要作用。进一步的体内研究可能会澄清这个问题。
To understand better how different genomic regions may confer pathogenicity for the coxsackievirus B (CVB), two intratypic CVB1 variants and a number of recombinant viruses were studied. Sequencing analysis showed 23 nucleotide changes between the parental non-pathogenic CVB1N and the pathogenic CVB1Nm. Mutations present in CVB1Nm were more conserved than those in CVB1N when compared to other CVB sequences. Inoculation in C3H/HeJ mice showed that the P1 region is critical for pathogenicity in murine pancreas and heart. The molecular determinants of disease for these organs partially overlap. Several P1 region amino acid differences appear to be located in the decay accelerating factor (DAF) footprint CVBs. CVB1N and CVB1Nm interacted with human CAR, but only CVB1N seemed to interact with human DAF, as determined using soluble receptors in a plaque reduction assay. However, the murine homologue Daf-1 did not interact with any virus assessed by haemagglutination. The results of this study suggest that an unknown receptor interaction with the virus play an important role in the pathogenicity of CVB1Nm. Further in vivo studies may clarify this issue.
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