Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses.
Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses.
复制标题
呼吸道感染的病原体，具有毒和减毒病毒。
DOI：
10.1186/1743-422x-4-22
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发表时间：
2007-02-27
期刊：
影响因子：
4.8
通讯作者：
Terajima, Masanori
中科院分区：
文献类型：
--
作者：
Hayasaka, Daisuke;Ennis, Francis A.;Terajima, Masanori
神经毒力痘苗病毒(VV)西部储备株(WR)的呼吸道感染会导致肺部急性感染，然后病毒传播到其他器官，导致小鼠死亡。致命性的机制还不是很清楚。在这项研究中，我们使用WR株和毒力较低的Wyeth株，分析了致死量和非致死量VV鼻腔感染后的病毒复制和宿主免疫反应。与惠氏菌株相比，WR菌株在肺和脑中的复制更活跃。然而，感染较高致死剂量和较低非致死剂量的WR菌株的小鼠大脑中的病毒滴度没有差异，这表明大脑中的病毒复制量不太可能是致死的唯一决定因素。WR菌株在原代小鼠肺细胞中的生长情况好于Wyeth菌株。与WR或Wyeth菌株的非致死性感染相比，WR菌株的致死性感染与肺内淋巴细胞数量减少和T细胞表型改变有关。致死性感染时，胸腺严重萎缩，CD4、CD8双阳性T细胞减少。这些结果表明，高剂量WR毒株鼻腔感染致死是由于病毒在感染早期在肺细胞内复制较多，免疫抑制，导致肺内病毒复制失控所致。
Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal doses of VV using the WR strain and the less virulent Wyeth strain. The WR strain replicated more vigorously in the lung and in the brain than the Wyeth strain. There were, however, no differences between the virus titers in the brains of mice infected with the higher lethal dose and the lower non-lethal dose of WR strain, suggesting that the amount of virus replication in the brain is unlikely to be the sole determining factor of lethality. The WR strain grew better in primary mouse lung cells than the Wyeth strain. Lethal infection with WR strain was associated with a reduced number of lymphocytes and an altered phenotype of the T cells in the lung compared to non-lethal infections with the WR or Wyeth strains. Severe thymus atrophy with a reduction of CD4 and CD8 double positive T cells was also observed in the lethal infection. These results suggest that the lethality induced by intranasal infection with a high dose of the WR strain is caused by the higher replication of virus in lung cells and immune suppression during the early phase of the infection, resulting in uncontrolled virus replication in the lung.