Cytopathogenesis of vesicular stomatitis virus is regulated by the PSAP motif of M protein in a species-dependent manner.
Cytopathogenesis of vesicular stomatitis virus is regulated by the PSAP motif of M protein in a species-dependent manner.
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囊泡口腔炎病毒的细胞致病发生受M蛋白的PSAP基序以物种依赖性方式调节。
DOI：
10.3390/v4091605
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发表时间：
2012-09
期刊：
影响因子：
--
通讯作者：
Harty RN
中科院分区：
文献类型：
--
作者：
Irie T;Liu Y;Drolet BS;Carnero E;García-Sastre A;Harty RN
水疱性口炎病毒（VSV）是一种重要的牛和马媒介传播病原体，引起可报告的水疱病。 VSV 的基质 (M) 蛋白具有多功能性，在细胞病变、细胞凋亡、宿主蛋白关闭和病毒粒子组装/出芽中发挥关键作用。我们之前的研究结果表明，M 蛋白内 37PSAP40 基序侧翼残基的突变导致 VSV 重组体在小鼠中具有减弱的表型。在本报告中，我们描述了两只小鼠、白纹伊蚊 C6/36 蚊子和库蠓 KC 细胞系中 VSV 重组 PS > A4（其包含四个丙氨酸 (AAAA) 代替 PSAP 基序，且不破坏侧翼残基）的表型。根据体重减轻、死亡率以及从受感染动物的肺和脑样本中测量的病毒滴度来判断，PS > A4重组体在受感染的小鼠中表现出减毒表型。然而，出乎意料的是，与对照病毒观察到的结果相比，PS > A4 重组体在昆虫 C6/36 细胞中表现出强烈的细胞病变表型。值得注意的是，在受感染的 C6/36 细胞和来自库蠓（一种已知的 VSV 载体物种）的 KC 细胞中，重组 PS > A4 的滴度比对照病毒的滴度高约 10 倍。此外，重组 PS > A4 诱导受感染的 C6/36 细胞中 C3 caspase 活性水平增加 25 倍。这些发现表明，PSAP 基序以物种依赖性方式在调节细胞致病性中发挥直接作用，并表明完整的 PSAP 基序可能对于维持 VSV 在昆虫宿主中的持久性很重要。
Vesicular stomatitis virus (VSV) is an important vector-borne pathogen of bovine and equine species, causing a reportable vesicular disease. The matrix (M) protein of VSV is multifunctional and plays a key role in cytopathogenesis, apoptosis, host protein shut-off, and virion assembly/budding. Our previous findings indicated that mutations of residues flanking the 37PSAP40 motif within the M protein resulted in VSV recombinants having attenuated phenotypes in mice. In this report, we characterize the phenotype of VSV recombinant PS > A4 (which harbors four alanines (AAAA) in place of the PSAP motif without disruption of flanking residues) in both mice, and in Aedes albopictus C6/36 mosquito and Culicoides sonorensis KC cell lines. The PS > A4 recombinant displayed an attenuated phenotype in infected mice as judged by weight loss, mortality, and viral titers measured from lung and brain samples of infected animals. However, unexpectedly, the PS > A4 recombinant displayed a robust cytopathic phenotype in insect C6/36 cells compared to that observed with control viruses. Notably, titers of recombinant PS > A4 were approximately 10-fold greater than those of control viruses in infected C6/36 cells and in KC cells from Culicoides sonorensis, a known VSV vector species. In addition, recombinant PS > A4 induced a 25-fold increase in the level of C3 caspase activity in infected C6/36 cells. These findings indicate that the PSAP motif plays a direct role in regulating cytopathogenicity in a species-dependent manner, and suggest that the intact PSAP motif may be important for maintaining persistence of VSV in an insect host.
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5.4
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