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Innate Recognition of Human Herpesviruses

对人类疱疹病毒的先天识别

基本信息

批准号：
9233912
负责人：
BLOSSOM A DAMANIA
金额：
$ 41.54万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9233912
关键词：
Acids Affect Africa South of the Sahara Binding Biochemical Cell Nucleus Cells Child Cytokine Gene DNA DNA Damage DNA Virus Infections DNA Viruses Data Double-Stranded RNA Endocytosis Exanthema Subitum Family Family member Genetic Transcription Genome Goals Herpesviridae Herpesviridae Infections Human Human Herpesvirus 6 Human Herpesvirus 8 Immune Immune response Immune system Immunity Infection Innate Immune Response Instruction Interferon-beta Interferons Kaposi Sarcoma Ligand Binding Ligands Luciferases Malignant Neoplasms Mediating Molecular Multicentric Angiofollicular Lymphoid Hyperplasia National Institute of Allergy and Infectious Disease Natural Immunity Nucleic Acid Binding Nucleic Acids Open Reading Frames Pathogenicity Pathway interactions Phosphotransferases Plasmids Population Primary Infection Proteins Proteomics Publishing RNA Reporter Role Site Supporting Cell TLR3 gene Transcript Untranslated RNA Up-Regulation Viral Viral Genome Viral Proteins Virus Virus Diseases Work extracellular knock-down macrophage scavenger receptors member men novel pathogen primary effusion lymphoma programs promoter receptor response sensor trafficking transcriptome

项目摘要

Human Herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) and human herpesvirus (HHV6) are members ofthe herpesvirus family and are included on the NIAID list of Emerging/Re-Emerging pathogens. HHV8/KSHV is associated with three different cancers in the human population including Kaposi's sarcoma (KS), primary effusion lymphoma and multicentric Castleman's disease. In Sub-Saharan Africa, KS is the most common cancer in men. Human herpesvirus type-6 (HHV-6) is the infectious cause of roseola infantum in young children. In response to RFA-AI-12-048, "Immune mechanisms of Viral Control, we propose to determine how DNA herpes viruses are sensed by the host immune system. We propose to determine the interaction of multiple pathogen recognition receptors (PRRs) with these DNA viruses and the mechanisms by which these viruses are sensed by host PRRs to activate the innate immune response. We hypothesize that PRRs involved in nucleic acid sensing of viral genomes are able to detect KSHV and HHV6 and activate innate immune responses. Additionally, the DNA damage response induced by herpes viral infection may also contribute to activation of innate immune pathways. This project advances the overall goals of the program by using cutting edge quantitative proteomic approaches to identify novel paradigm shifting pathways of pathogen sensing, identifying nucleic acid binding by human PRRs, and determining cross-talk between multiple PRRs in the host response to NIAID Emerging/Reemerging viruses.

人类疱疹病毒 8 (HHV8)，也称为卡波西肉瘤相关疱疹病毒 (KSHV) 和人类疱疹病毒 (HHV6)，是疱疹病毒家族的成员，并被列入 NIAID 新发/再发病原体清单。 HHV8/KSHV 与人类中的三种不同癌症相关，包括卡波西肉瘤 (KS)、原发性渗出性淋巴瘤和多中心卡斯尔曼病。在撒哈拉以南非洲地区，KS 是男性最常见的癌症。 6 型人类疱疹病毒 (HHV-6) 是幼儿玫瑰疹的传染源。针对 RFA-AI-12-048，“病毒控制的免疫机制，我们建议确定宿主免疫系统如何感知 DNA 疱疹病毒。我们建议确定多种病原体识别受体 (PRR) 与这些 DNA 病毒的相互作用，以及宿主 PRR 感知这些病毒以激活先天免疫反应的机制。我们假设 PRR 参与核酸病毒基因组的酸感应能够检测 KSHV 和 HHV6 并激活先天免疫反应。此外，疱疹病毒感染引起的 DNA 损伤反应也可能有助于激活先天免疫途径。该项目通过使用最先进的定量蛋白质组学方法来确定病原体传感的新范式转变途径、识别人类的核酸结合，从而推进了该计划的总体目标 PRR，并确定宿主对 NIAID 新出现/重新出现病毒的反应中多个 PRR 之间的串扰。