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）：疱疹感染代表了世界上最常见的病毒感染之一。这些病毒可以是亚临床的，也可以如卡波西肉瘤相关的疱疹病毒（KSHV）而导致危险疾病（例如癌症）。 KSHV在艾滋病患者中众所周知会导致卡波西肉瘤（KS）和其他几种淋巴增生性疾病。这些病毒在口腔中设置感染，可以口服传播。该应用程序的总体目标是定义KSHV之间的相互作用 和先天的免疫反应在口腔中引起感染细胞的病毒。我们将重点介绍对KSHV感染的先天免疫反应，尤其是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将其放置方式阻止或使用该系统来增强其在宿主中的复制。该项目的目的是导致开发新颖的，先天免疫的治疗剂，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）的组，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。此应用程序 设置以确定这些系统如何相互作用以导致感染和疾病。该R03赠款的长期工作将设置初步数据，以申请较大的R01赠款 探索如何调节这些机制以抵抗KSHV感染和相关疾病。