Gaccione C, Marcus P I
Department of Molecular and Cell Biology, University of Connecticut, Storrs 06269-3004.
J Interferon Res. 1989 Oct;9(5):603-14. doi: 10.1089/jir.1989.9.603.
In contrast to wild-type vesicular stomatitis virus (VSV) of Indiana (Ind.) origin which express interferon (IFN) inducing- and IFN induction-suppressing activities as mutually exclusive properties, individual particles of wild-type VSV of the New Jersey (N.J.) serotype (Hazelhurst [H] isolate) paradoxically can both induce IFN and suppress its induction in cells coinfected with a potent inducer of IFN. The properties of IFN induction, and its suppression, appear to reside in the particle that manifests infectivity. Analyses of IFN induction dose-response curves to measure IFN-inducing particles (IFP), and IFN yield-reduction curves to measure IFN induction-suppressing particles (ISP) generated by VSV-N.J.(H) in aged chick embryo cells revealed that (i) a single particle per cell sufficed to induce a quantum (full) yield of IFN, or to suppress fully IFN production by a coinfecting inducing virus, and (ii) the addition of one or more IFP per cell did not suppress the yield of IFN beyond the plateau level. The time-course of IFN production in chick cells infected with VSV-N.J. (H) revealed about a 4-h lag, even when the cells were coinfected with a potent inducer that normally induced IFN 1 or 2 h sooner. Thus, VSV-N.J.(H) appears to regulate the production of IFN in cells--even that initiated by other inducers. Expression of IFP and ISP activities both required primary transcription, with respective genomic targets similar to those reported for VSV-Ind. N.J.(H) is the first wild-type VSV observed to express IFP and ISP activities concomitantly. A model is presented to suggest how these two antagonistic properties might be expressed by a single infectious particle.
与源自印第安纳州(Ind.)的野生型水疱性口炎病毒(VSV)不同,后者将干扰素(IFN)诱导活性和IFN诱导抑制活性作为互斥特性来表达,新泽西州(N.J.)血清型的野生型VSV(黑泽赫斯特[H]分离株)的单个颗粒却自相矛盾地既能诱导IFN,又能在与强效IFN诱导剂共感染的细胞中抑制IFN的诱导。IFN诱导及其抑制特性似乎存在于具有感染性的颗粒中。对VSV-N.J.(H)在老龄鸡胚细胞中产生的用于测量IFN诱导颗粒(IFP)的IFN诱导剂量反应曲线和用于测量IFN诱导抑制颗粒(ISP)的IFN产量降低曲线的分析表明:(i)每个细胞一个颗粒足以诱导出定量(完全)的IFN产量,或完全抑制共感染的诱导病毒产生的IFN,并且(ii)每个细胞添加一个或多个IFP不会使IFN产量降低到平台水平以下。用VSV-N.J.(H)感染鸡细胞时IFN产生的时间进程显示有大约4小时的延迟,即使细胞与通常能提前1或2小时诱导IFN的强效诱导剂共感染也是如此。因此,VSV-N.J.(H)似乎能调节细胞中IFN的产生——甚至是由其他诱导剂引发的IFN产生。IFP和ISP活性的表达都需要初级转录,各自的基因组靶点与VSV-Ind报道的相似。N.J.(H)是观察到的首个同时表达IFP和ISP活性的野生型VSV。本文提出了一个模型,以说明单个感染性颗粒如何表达这两种拮抗特性。