Tissue tropism of recombinant coxsackieviruses in an adult mouse model
Tissue tropism of recombinant coxsackieviruses in an adult mouse model
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DOI：
10.1099/vir.0.80603-0
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发表时间：
2005-07-01
影响因子：
3.8
通讯作者：
Hyypiä, T
中科院分区：
文献类型：
--
作者：
Harvala, H;Kalimo, H;Hyypiä, T
通过交换5'非编码区（5' NCR）、结构蛋白和非结构蛋白编码序列构建重组病毒，研究了柯萨奇病毒A9（CAV 9）和柯萨奇病毒B3（CBV 3）感染成年小鼠和两种细胞系的差异决定因素。来自成年BALB/c小鼠的不同组织的重组病毒和亲本病毒的空斑测定滴定表明，CBV 3的结构区域由于受体识别而确定了对肝组织的向性，并且CBV 3的5 'NCR增强了小鼠胰腺中的病毒增殖。感染嵌合病毒，含有结构区从CBV 3和其余的基因组从CAV 9，和亲本CBV 3株，引起高水平的病毒血症在成年小鼠。这些病毒感染中枢神经系统的能力表明，嗜神经性与高复制水平和CBV 3衣壳蛋白的存在有关，这也增强了中和抗体的形成。此外，中和抗体的出现与病毒从组织中的清除直接相关。这些结果表明，种内重组柯萨奇病毒的潜在致病性，和组织嗜性的遗传决定因素的复杂性。
Recombinant viruses, constructed by exchanging the 5' non-coding region (5'NCR), structural and non-structural protein coding sequences were used to investigate determinants responsible for differences between coxsackievirus A9 (CAV9) and coxsackievirus B3 (CBV3) infections in adult mice and two cell lines. Plaque assay titration of recombinant and parental viruses from different tissues from adult BALB/c mice demonstrated that the structural region of CBV3 determined tropism to the liver tissue due to receptor recognition, and the 5'NCR of CBV3 enhanced viral multiplication in the mouse pancreas. Infection with a chimeric virus, containing the structural region from CBV3 and the rest of the genome from CAV9, and the parental CBV3 strain, caused high levels of viraemia in adult mice. The ability of these viruses to infect the central nervous system suggested that neurotropism is associated with high replication levels and the presence of the CBV3 capsid proteins, which also enhanced formation of neutralizing antibodies. Moreover, the appearance of neutralizing antibodies correlated directly with the clearance of the viruses from the tissues. These results demonstrate potential pathogenicity of intraspecies recombinant coxsackieviruses, and the complexity of the genetic determinants underlying tissue tropism.