Gene expression analysis of HSV-1 infected cells

描述（由申请人提供）：1型单纯疱疹病毒（HSV-1）是一种人类病原体，可引起口面病变、角结膜炎和脑炎等疾病。在外周部位初次感染后，病毒在感觉神经元中建立潜伏期。潜伏病毒的再活化导致疱疹性疾病的复发。这项研究的重点是检查HSV-1感染对细胞过程的影响，这些细胞过程可能影响HSV-1感染的成功或失败。利用DMA微阵列识别基因和途径转录改变病毒感染，我们将表征这些细胞途径在感染中的作用，以及病毒如何逃避或修改细胞反应。我们目前的研究重点是体内感染模型。此外，将纳入缺乏ICP34.5的HSV-1突变体，以比较对小鼠角膜中严重减毒病毒的细胞应答。我们从感染角膜的初步结果表明，许多病毒类型的具体变化，最值得注意的是，突变病毒诱导细胞基因表达在3 dpi的变化很少，并显示出减少诱导宿主免疫反应。我们计划在小鼠角膜中比较病毒复制和传播以及宿主免疫应答，以构建角膜模型中病毒生命周期和宿主应答的范例。单纯疱疹病毒经常引起各种综合征，从唇疱疹和生殖器溃疡，到更严重的致盲性眼病，以及潜在的致命性脑感染。该病毒对治愈具有抗药性，尽管有抗病毒药物，但仍继续造成严重问题。这项工作将使人们更好地了解病毒是如何引起疾病的，并将为改进针对这种重要病原体的疗法和疫苗铺平道路。

DESCRIPTION (provided by applicant): Herpes simplex virus type 1 (HSV-1) is a human pathogen responsible for diseases such as orofacial lesions, keratoconjunctivitis, and encephalitis. Following primary infection at a peripheral site, the virus establishes latency in sensory neurons. Reactivation of latent virus results in recurrent herpetic disease. The focus of this research is to examine the effects of HSV-1 infection on cellular processes that could impact the success or failure of HSV-1 infection. Utilizing DMA microarrays to identify genes and pathways transcriptionally altered by viral infection, we will characterize the roles these cellular pathways have in infection, and how the virus evades or modifies the cellular response. Our current research focuses on an in vivo model of infection. In addition, an HSV-1 mutant lacking ICP34.5 will be included to compare the cellular response to a virus that is severely attenuated in mouse corneas. Our preliminary results from infected corneas show numerous virus-type specific changes, most notable that the mutant virus induces few changes in cellular gene expression at 3 dpi, and shows a decreased induction of the host immune response. We plan to compare viral replication and spread and the host immune response in mouse corneas, in order to construct a paradigm of the viral life cycle and host response in the corneal model. Herpes simplex viruses frequently cause a variety of syndromes from cold sores and genital sores, to more serious blinding ocular diseases, and potentially fatal brain infections. The virus is resistant to cure, and continues to cause severe problems despite the availability of antiviral drugs. This work will allow a better understanding of how the virus causes disease, and will pave the way towards improved therapies and vaccines against this significant pathogen.