Prescott Joseph, Ye Chunyan, Sen Ganes, Hjelle Brian
Infectious Diseases and Inflammation Program, Dept. of Pathology, University of New Mexico, University of New Mexico, Albuquerque, NM 87131-0001, USA.
J Virol. 2005 Dec;79(24):15007-15. doi: 10.1128/JVI.79.24.15007-15015.2005.
Maladaptive immune responses are considered to be important factors in the pathogenesis of the two diseases caused by hantaviruses, hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome (HCPS). While the intensity of adaptive antiviral T-cell responses seems to correlate with the severity of HCPS, there is increasing evidence that innate antiviral responses by endothelial cells, the native targets for hantavirus infection in vivo, are induced within hours of exposure to infectious hantaviruses. To investigate early events in the innate response to Sin Nombre virus (SNV), the principal etiologic agent of HCPS in North America, we treated human endothelial cells with live virus, or virus subjected to inactivation by UV irradiation at minimal doses required to inhibit replication, and assayed host expression of interferon-stimulated genes (ISG) by microarray and reverse transcription-PCR. We show herein that a variety of ISG are induced between 4 and 24 h after exposure to both live and killed virus. The levels of such induction at early time points (before 24 h) were generally higher in cells treated with SNV particles that had been killed by exposure to UV irradiation. Additionally, SNV exposed to increasing doses of UV irradiation induced ISG better than live virus despite increased disruption of viral RNA integrity. However, SNV replication was required for continued ISG overexpression by 3 days posttreatment. These results suggest that hantavirus particles may themselves be capable of early induction of ISG and that ongoing production of viral particles during infection could contribute to the pathogenic process.
适应性免疫反应被认为是由汉坦病毒引起的两种疾病（肾综合征出血热和汉坦病毒心肺综合征，即HCPS）发病机制中的重要因素。虽然适应性抗病毒T细胞反应的强度似乎与HCPS的严重程度相关，但越来越多的证据表明，内皮细胞（体内汉坦病毒感染的天然靶标）的先天性抗病毒反应在接触传染性汉坦病毒数小时内就会被诱导。为了研究对北美HCPS的主要病原体辛诺柏病毒（SNV）先天性反应的早期事件，我们用活病毒或经紫外线照射灭活的病毒（以抑制复制所需的最小剂量）处理人内皮细胞，并通过微阵列和逆转录聚合酶链反应检测干扰素刺激基因（ISG）的宿主表达。我们在此表明，在接触活病毒和灭活病毒后4至24小时之间会诱导多种ISG。在早期时间点（24小时之前），用紫外线照射灭活的SNV颗粒处理的细胞中这种诱导水平通常更高。此外，尽管病毒RNA完整性的破坏增加，但暴露于增加剂量紫外线照射的SNV比活病毒诱导ISG的效果更好。然而，在处理后3天持续的ISG过表达需要SNV复制。这些结果表明，汉坦病毒颗粒本身可能能够早期诱导ISG，并且感染期间病毒颗粒的持续产生可能有助于致病过程。
