Budding site of Sendai virus in polarized epithelial cells is one of the determinants for tropism and pathogenicity in mice.
Budding site of Sendai virus in polarized epithelial cells is one of the determinants for tropism and pathogenicity in mice.
复制标题
仙台病毒在极化上皮细胞中的出芽位点是小鼠向性和致病性的决定因素之一。
DOI：
10.1016/0042-6822(92)90443-s
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发表时间：
1992
期刊：
影响因子：
3.7
通讯作者：
Rott,R
中科院分区：
文献类型：
--
作者：
Tashiro,M;Seto,JT;Choosakul,S;Yamakawa,M;Klenk,HD;Rott,R
野生型仙台病毒融合(F)糖蛋白在体外和体内分别需要胰蛋白酶或胰蛋白酶样蛋白酶进行裂解激活。该病毒在小鼠体内呈嗜肺性，在支气管上皮细胞的顶端产生芽。另一方面，蛋白酶激活宿主范围突变体F1-R的F蛋白被存在于不同细胞系和小鼠各器官中的普遍存在的蛋白酶切割。F1 -R在小鼠中引起全身性感染，突变芽在感染上皮细胞的顶端和底外侧区域呈两极分化。F1 -R中F蛋白的可切割性增强已被证明是泛向性的主要决定因素。此外，有假设认为F1 -R的双极出芽是病毒全身传播所必需的，这被归因于F1 -R基质(M)蛋白的突变（Tashiroet al.,Virology184, 227 - 234,1991）。本研究从野生型病毒中分离到蛋白酶激活突变体（KD系列）。结果显示，它们在顶端区域萌发，F蛋白被小鼠器官中普遍存在的蛋白酶切割。KD突变体在小鼠鼻内感染后仅嗜气性，而直接接种到循环系统时则引起全身性感染。对KD突变体的F基因的比较核苷酸序列分析显示，推断出的负责增强F蛋白可切割性的氨基酸替换发生在切割位点之外。在分析的KD突变体的M基因中根本没有发现突变，这支持了F1 -R的M蛋白和来自后者的可逆T-9在双极出芽中的作用。这些结果表明，双极出芽是Fl-R从肺部全身传播的必要条件，野生型病毒和KD突变体的根尖出芽导致呼吸道感染。因此，除了小鼠器官中F蛋白的裂解激活外，在感染的主要目标处的差异出芽也是仙台病毒在小鼠中的嗜性和致病性的决定因素。
Wild-type Sendai virus fusion (F) glycoprotein requires trypsin or a trypsin-like protease for cleavage-activationin vitroandin vivo, respectively. The virus is pneumotropic in mice and buds at the apical domain of bronchial epithelial cells. On the other hand, the F protein of the protease-activation host range mutant, F1-R, is cleaved by ubiquitous proteases present in different cell lines and in various organs of mice. F1 -R causes a systemic infection in mice and the mutant buds bipolarly at the apical and basolateral domains of infected epithelial cells. The enhanced cleavability of the F protein of F1 -R has been shown to be a primary determinant for pantropism. Additionally, it has been postulated that bipolar budding of F1 -R is required for the systemic spread of the virus and it has been attributed to mutations in the matrix (M) protein of F1 -R (Tashiroet al.,Virology184, 227–234, 1991). In this study protease-activation mutants (KD series) were isolated from wild-type virus. They were revealed to bud at the apical domain, and the F protein was cleaved by ubiquitous proteases in mouse organs. The KD mutants were exclusively pneumotropic in mice following intranasal infection, whereas they caused a generalized infection when inoculated directly into the circulatory system. Comparative nucleotide sequence analyses of the F gene of the KD mutants revealed that the deduced amino acid substitutions responsible for enhanced cleavability of the F protein occurred removed from the cleavage site. Mutations were not at all found in the M gene of the KD mutants analyzed, in support of the role of the M protein of F1 -R and of a revertant T-9 derived from the latter in bipolar budding. These results suggest that bipolar budding is necessary for the systemic spread of Fl-R from the lungs and that apical budding by wild-type virus and the KD mutants leads to respiratory infections. Differential budding at the primary target of infection, in addition to the cleavage-activation of the F protein in mouse organs, is therefore also a determinant for tropism and pathogenicity of Sendai virus in mice.