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Modulation of Innate Immunity by KSHV

KSHV 对先天免疫的调节

基本信息

批准号：
10421081
负责人：
BLOSSOM A DAMANIA
金额：
$ 41.29万
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：
2018
资助国家：
美国
起止时间：
2018-09-11 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10421081
关键词：
Antiviral Response Binding Cell Culture Techniques Cells Cyclic GMP DNA DNA Viruses Development Dinucleoside Phosphates Disease Gene Activation Genes HIV HIV Infections HIV Seronegativity Human Human Herpesvirus 8 Immune Immune response Immune system Immunosuppression In Vitro Incidence Individual Infection Innate Immune Response Interferons Kaposi Sarcoma Life Liquid substance Lymphoma Malignant Neoplasms Mediating Natural Immunity Oral Oral cavity Palate Kaposi&apos s Sarcoma Pathogenesis Pathogenicity Pathway interactions Patients Periodicity Play Population Primary Infection Production Proteins Reporting Role Route Saliva Sexual Transmission Signal Transduction Stimulator of Interferon Genes Sum Symptoms Syndrome Therapeutic immunosuppression Time Toll-like receptors Transplant Recipients Viral Viral Genes Viral Genome Viral Pathogenesis Viral Proteins Virus Virus Inhibitors antiretroviral therapy base cell type co-infection immune reconstitution in vivo innate immune pathways macrophage microorganism monocyte prevent reactivation from latency receptor recombinant virus response sarcoma sensor viral interferon regulatory factor-1

项目摘要

PROJECT ABSTRACT KSHV is both a commensal and pathogenic microorganism in the human host. Many studies have shown that KSHV is present in the saliva and oral cavity and can be transmitted through both oral and sexual transmission routes. In conditions of immune suppression e.g. HIV infection or immunosuppressive therapy, KSHV is associated with the development of sarcomas and lymphomas, including in the oral cavity. Although these diseases are usually seen in the context of immune suppression, even HIV- negative individuals can develop KSHV-associated cancers. Thus, it is clear that the host immune system plays a critical role in preventing diseases associated with KSHV infection. It is currently unclear how the immune system keeps KSHV in check in healthy individuals, but allows disease to progress during times of immunosuppression. We have previously reported that TLRs, RLRs and NLRs are capable of detecting KSHV in a variety of different biologically relevant cell types during primary infection and during reactivation from latency. We also reported that the cGAS-STING DNA sensing pathway can detect KSHV during primary infection and reactivation and that KSHV viral proteins can counteract activation of this important pathway. In this application, we propose to determine how KSHV viral proteins modulate cGAS and STING innate immune proteins and allow the virus to successfully establish life-long latency in the human host. We also propose to examine how KSHV's modulation of innate immune pathways impacts HIV infection.

项目摘要 KSHV是人类宿主中的一种寄生性和致病性微生物。许多研究表明，KSHV存在于唾液和口腔中，通过口腔和性传播途径传播。在免疫条件下抑制，例如HIV感染或免疫抑制治疗，KSHV与肉瘤和淋巴瘤的发展，包括在口腔中。虽然这些疾病通常是在免疫抑制的情况下出现的，甚至是艾滋病毒- 阴性个体可发展为KSHV相关的癌症。显然，宿主免疫系统在预防与KSHV相关的疾病中起关键作用感染目前尚不清楚免疫系统如何保持KSHV在检查健康个体，但允许疾病在免疫抑制期间进展。我们有先前报道TLR、RLR和NLR能够检测KSHV，各种不同的生物学相关的细胞类型在原发性感染和从潜伏期重新激活。我们还报道了cGAS-STING DNA传感 KSHV信号通路可以在初次感染和再激活期间检测KSHV，蛋白质可以抵消这一重要途径的激活。在本申请中，我们建议确定KSHV病毒蛋白如何调节cGAS和STING先天性免疫蛋白，并允许病毒成功地建立终身潜伏在人类宿主我们还建议研究KSHV如何调节先天免疫，途径影响艾滋病毒感染。