Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis
Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis
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DOI：
10.1128/jvi.75.10.4692-4698.2001
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发表时间：
2001-05-01
影响因子：
5.4
通讯作者：
Peterhans, E
中科院分区：
文献类型：
--
作者：
Schweizer, M;Peterhans, E
牛病毒性腹泻病毒(BVDV)是黄病毒科的一种疫病病毒，是一种具有重要经济意义的牛病原，广泛分布于世界各地。BVDV的非细胞病态(Ncp)和细胞病态(Cp)两种生物型都可以从患有这种致命粘膜疾病的持续感染的牛身上分离出来。Cp生物型与NS3非结构蛋白的产生有关，在相应的NCP生物型中，NS3以未被切割的形式存在。以前，我们已经证明Cp而不是NCP BVDV可以诱导牛巨噬细胞中AIP干扰素的形成。在这项研究中，我们证明了NCP BVDV抑制了人工合成的双链RNA聚(IC)诱导的细胞凋亡和干扰素α/β的表达。NCP BVDV仅在加入dsRNA至少12h前感染NCP BVDV的细胞中观察到抑制作用，这表明NCP病毒需要病毒蛋白的表达来抑制Poly(IC)的作用。进一步的实验表明，NCP BVDV干扰了dsRNA的细胞内作用，而不是干扰了它在细胞内的摄取。NCP BVDV感染细胞对放线菌素D或星形孢子素诱导的细胞凋亡无抵抗力，提示NCP BVDV可能通过dsRNA特异性干扰信号传导，对先天抗病毒宿主反应的干扰可能解释了NCP BVDV在胎儿发育早期成功建立持续感染的原因。
Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal disease. The cp biotype correlates with the production of the NS3 nonstructural protein, which in the corresponding ncp biotype is present in its uncleaved form, NS23, Previously, we have shown that cp hut not ncp BVDV induces the formation of aip interferons in bovine macrophages. In this study, we demonstrate that ncp BVDV inhibits the induction of apoptosis and the expression of interferon alpha/beta by poly(IC), a synthetic double-stranded RNA (dsRNA). Inhibition was observed only in cells which had been infected with ncp BVDV at least 12 h prior to the addition of dsRNA, which indicates that expression of viral proteins is necessary for the ncp virus to inhibit the effects of poly(IC), Additional experiments using transfected poly(IC) showed that ncp BVDV interfered with the intracellular action of dsRNA rather than with its uptake into the cells. Infected cells were not resistant to induction of apoptosis by actinomycin D or staurosporine, which suggests that ncp BVDV may specifically interfere with signaling through dsRNA, Interference with the innate antiviral host responses may explain the successful establishment of persistent infection by ncp BVDV in fetuses early in their development.