Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus

Differential expression of the immediate-early 2 and 3 proteins in developing mouse brains infected with murine cytomegalovirus
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DOI:
10.1007/s00705-006-0793-0
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发表时间:
2006-11-01
影响因子:
2.7
通讯作者:
Tsutsui, Y.
Tsutsui, Y.
中科院分区:
医学4区
文献类型:
--
作者:
Ishiwata, M.;Baba, S.;Tsutsui, Y.

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小鼠巨细胞病毒(MCMV)立即早期(IE)2蛋白已被报道可抑制小鼠的生长和潜伏期。因此,其在病毒发病机制和组织嗜性中的作用尚不清楚。在这里,我们通过使用在大肠杆菌中表达的融合蛋白作为抗原制备了针对IE2和IE3蛋白的特异性抗体。MCMV感染培养的成纤维细胞的免疫染色显示IE2蛋白在核质中广泛表达,类似于IE1蛋白。与此相反,IE3蛋白,88 kDa的表达,在感染的早期阶段,在细胞核中表现出点状图案,然后减少。在MCMV感染的新生小鼠脑中,免疫组化检测到IE2和IE3蛋白在感染早期的心室壁细胞中。当感染时间延长时,IE2蛋白在皮层和海马的神经元中表达,而IE3蛋白在感染早期优先在胶质细胞中表达,并且其水平在感染期间下降。这些结果表明,IE2蛋白可能在神经元中的持续感染中发挥作用,而IE3蛋白,优先在胶质细胞中表达,可能在急性感染中发挥主要作用。
Murine cytomegalovirus (MCMV) immediate-early (IE) 2 protein has been reported to be dispensable for growth and latency in mice. Therefore, its role in viral pathogenesis and tissue tropism is not known. Here we prepared specific antibodies to the IE2 and IE3 proteins by using fusion proteins expressed in Escherichia coli as antigens. Immunostaining of MCMV-infected cultured fibroblasts revealed IE2 protein to be expressed diffusely in the nucleoplasm similar to the IE1 protein. In contrast, expression of the IE3 protein, 88 kDa, exhibited a punctate pattern in the nucleus in the early phase of infection then diminished. In the brain of neonatal mice infected with MCMV, both IE2 and IE3 proteins were detected immunohistochemically in the cells of the ventricular walls early in infection. When the infection was prolonged, the IE2 protein was expressed in neurons of the cortex and hippocampus, while the IE3 protein was preferentially expressed in glial cells in the early phase of infection, and its levels declined during the infection. These results suggest that the IE2 protein may play a role in persistent infection in neurons, whereas the IE3 protein, expressed preferentially in glial cells, may play the main role in acute infection.