Harvala Heli, Kalimo Hannu, Bergelson Jeffrey, Stanway Glyn, Hyypiä Timo
Department of Virology and MediCity Research Laboratory, University of Turku, FIN-20520 Turku, Finland.
Department of Pathology, University of Uppsala, Uppsala, Sweden.
J Gen Virol. 2005 Jul;86(Pt 7):1897-1907. doi: 10.1099/vir.0.80603-0.
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.
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的重组病毒，用于研究导致柯萨奇病毒A9（CAV9）和柯萨奇病毒B3（CBV3）在成年小鼠和两种细胞系中感染差异的决定因素。对成年BALB/c小鼠不同组织中的重组病毒和亲本病毒进行空斑试验滴定表明，CBV3的结构区域由于受体识别决定了对肝脏组织的嗜性，而CBV3的5'NCR增强了病毒在小鼠胰腺中的增殖。用含有CBV3结构区域和CAV9基因组其余部分的嵌合病毒以及亲本CBV3毒株感染成年小鼠，导致了高水平的病毒血症。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CBV3衣壳蛋白的存在有关，CBV3衣壳蛋白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。这些结果证明了种内重组柯萨奇病毒的潜在致病性，以及组织嗜性背后遗传决定因素的复杂性。
