KSHV Modulation of Type I Interferon

I 型干扰素的 KSHV 调节

• 批准号: 8662232
• 负责人: DAVID JESSE SANCHEZ
• 金额: $ 10.95万
• 依托单位: WESTERN UNIVERSITY OF HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-15 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8662232
• 关键词: Acquired Immunodeficiency Syndrome; Adaptor Signaling Protein; Affect; Africa South of the Sahara; Amino Acid Sequence; Antiviral Agents; Award; Biochemical; Cancerous; Cells; Clinical; DNA; DNA Structure; Data; Development; Disease; Dominant-Negative Mutation; Family; Foundations; Funding; Future; Genome; Genomic DNA; Goals; Grant; Growth; Herpesviridae; Herpesviridae Infections; Human; Human Herpesvirus 8; Immune; Immune response; Immune system; Immunocompromised Host; Individual; Infection; Inflammatory; Interferon Type I; Interferon Type II; Interferons; Kaposi Sarcoma; Knowledge; Laboratories; Lead; Lymphoproliferative Disorders; Malignant Neoplasms; Maps; Molecular; Names; Natural Immunity; Nucleic Acids; Open Reading Frames; Oral cavity; Oral mucous membrane structure; Pathogenesis; Pathway interactions; Patients; Pattern; Peptide Sequence Determination; Phase; Production; Proteins; Research; Research Personnel; Saliva; Side; Signal Induction; Signal Transduction; Site; Structure; System; Therapeutic; Viral; Virus; Virus Diseases; Work; base; fighting; gammaherpesvirus; member; men; mucosal site; novel; pandemic disease; pathogen; public health relevance; receptor; receptor function; response; sound; tool; transmission process; viral DNA

DESCRIPTION (provided by applicant): Herpes infections represent one of the most common viral infections that exist in the world. These viruses can be subclinical or as in the case of Kaposi's Sarcoma Associated Herpesvirus (KSHV) they can lead to dangerous diseases such as cancer. KSHV is well known in AIDS patients to cause Kaposi's Sarcoma (KS) and several other lymphoproliferative diseases. These viruses setup infection in oral cavities and can be transmitted orally. The overall goal of this application is to define the interactions between KSHV and the innate immune response the virus elicits in infected cells in the oral cavity. We will focu on the innate immune response to KSHV infection, especially the Type I Interferon response. Type I Interferon is well known to be the body's natural anti-viral system and almost all viruses that cause infection in humans have devolved ways to block or use this system to enhance their replication in the host. The goal of this project is to lead to the development of novel, innate immune based therapeutics harnessing the power of the innate immune system to directly stop KSHV replication. We were the first group to determine how the innate immune system can recognize herpesviruses (including KSHV) and have also defined the signaling mechanisms that induce interferon (from the host side) and block interferon (from the virus side). This application is setup to determine how these systems interact together to lead to infection and disease. Long term work from this R03 grant will setup preliminary data to apply for a larger R01 grant that will explore how these mechanisms can be modulated to fight KSHV infection and associated diseases.

描述（由申请人提供）：疱疹感染是世界上最常见的病毒感染之一。这些病毒可能是亚临床的，也可能像卡波西肉瘤相关疱疹病毒 (KSHV) 那样，导致癌症等危险疾病。众所周知，KSHV 在艾滋病患者中会引起卡波西肉瘤 (KS) 和其他几种淋巴组织增生性疾病。这些病毒会在口腔中引起感染，并可以通过口腔传播。该应用程序的总体目标是定义 KSHV 之间的交互 以及病毒在口腔受感染细胞中引发的先天免疫反应。我们将重点关注 KSHV 感染的先天免疫反应，特别是 I 型干扰素反应。众所周知，I 型干扰素是人体的天然抗病毒系统，几乎所有引起人类感染的病毒都已发展出阻止或使用该系统来增强其在宿主中复制的方法。该项目的目标是开发基于先天免疫的新型疗法，利用先天免疫系统的力量直接阻止 KSHV 复制。我们是第一个确定先天免疫系统如何识别疱疹病毒（包括 KSHV）的小组，并且还定义了诱导干扰素（来自宿主侧）和阻断干扰素（来自病毒侧）的信号传导机制。这个应用程序 其目的是确定这些系统如何相互作用从而导致感染和疾病。这项 R03 赠款的长期工作将建立初步数据，以申请更大的 R01 赠款，这将 探索如何调节这些机制来对抗 KSHV 感染和相关疾病。