Mechanisms of KSHV Transmission

KSHV 传播机制

基本信息

批准号：
10598043
负责人：
BLOSSOM A DAMANIA
金额：
$ 58.37万
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：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598043
关键词：
Acquired Immunodeficiency Syndrome Affect Africa South of the Sahara Antibodies Area B-Lymphocytes Bacteria Biological Biological Assay Biology Body Fluids Butyrates CD19 gene Cell Line Childhood Clinical Clinical Research Clinical Trials Cohort Studies Country Cytomegalovirus DNA copy number Dedications Disease Encapsulated Epidemic Future Genes Genome Goals Herpesviridae Herpesviridae Infections Human Human Herpesvirus 4 Human Herpesvirus 8 Human Milk Immune In Vitro Individual Infant Infection Infectious Agent Innate Immune Response Intervention Life Life Cycle Stages Maps Measures Methylation Modeling Molecular Mothers Mucous Membrane Natural Immunity Oral Oral cavity Patients Persons Phenotype Plaque Assay Plasma Population Predisposition Research Design Risk Factors Route Saliva Salivary Sample Size Sampling Seminal fluid Seroprevalences Serum Shapes Single Nucleotide Polymorphism Specimen Surface Testing Vaccine Design Variant Viral Viral Genome Viral Load result Virus Diseases Volatile Fatty Acids cohort epidemiology study experimental study in vivo infected B cell keratinocyte laboratory experiment men who have sex with men microbiome microbiome signature novel oral microbiome prospective reactivation from latency reproductive transmission process tumor whole genome

项目摘要

Project Summary Abstract Kaposi's Sarcoma-associated herpesvirus is transmitted primarily by saliva, though other routes including semen and breastmilk have also been described. There exists a big discrepancy in KSHV seroprevalence across different populations. It is less than 10% in the US, but > 50% in KSHV endemic regions in Sub-Saharan Africa. Whereas the US AIDS-KS epidemic was driven by repeated contact among MSM, in endemic regions KSHV is acquired in childhood. We are responding to RFA-CA-18- 013 to decipher how KSHV is transmitted. The overall goal of this application is to understand the transmission of KSHV in molecular terms, with the ultimate goal being to inform vaccine design and identify other means of disrupting transmission. To achieve this goal, we will investigate the three pillars of transmissibility of infectious agents: (i) variance among KSHV strains using existing specimens from large clinical cohorts, (ii) variance among the innate immune responses to KSHV infection, and (iii) variance in the microbiome which may affect both KSHV itself (as measured by local viral load) and the innate immune response to infection. In each case, we will start by profiling natural human variation and then explore the function of significant viral and host variants in functional assays for entry, replication and transmission.

项目概要摘要卡波西肉瘤相关疱疹病毒主要通过唾液传播，但也有其他途径还描述了包括精液和母乳的情况。 KSHV存在较大差异不同人群的血清流行率。在美国，这一比例低于 10%，但在 KSHV 流行病中，这一比例高于 50% 撒哈拉以南非洲地区。而美国 AIDS-KS 的流行是由反复接触引起的在 MSM 中，在流行地区 KSHV 是在儿童时期获得的。我们正在回复 RFA-CA-18- 013 破译 KSHV 的传输方式。该应用程序的总体目标是了解 KSHV 在分子方面的传播，最终目标是为疫苗设计和确定其他中断传输的方法。为了实现这一目标，我们将研究三大支柱传染性病原体的传播能力：（i）使用现有样本的 KSHV 毒株之间的差异大型临床队列，(ii) 对 KSHV 感染的先天免疫反应之间的差异，以及 (iii) 微生物组的差异可能会影响 KSHV 本身（通过当地病毒载量测量）和对感染的先天免疫反应。在每种情况下，我们都将从分析人类自然变异开始然后探索重要病毒和宿主变异在进入功能分析中的功能，复制和传播。