Mechanisms of KSHV Transmission

KSHV 传播机制

基本信息

批准号：
9765479
负责人：
BLOSSOM A DAMANIA
金额：
$ 52.73万
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 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9765479
关键词：
Acquired Immunodeficiency Syndrome Affect Africa South of the Sahara Antibodies Area B-Lymphocytes Bacteria Biological Biological Assay Biology Butyrates CD19 gene Cell Line Childhood Clinical Clinical Research Clinical Trials Cohort Studies Country Cytomegalovirus DNA copy number 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 Liquid substance Maps Measures Methylation Modeling Molecular Mothers Mucous Membrane Natural Immunity Nucleotides Oral Oral cavity Patients Persons Phenotype Plaque Assay Plasma Population Research Design Risk Factors Route Saliva Salivary Sample Size Sampling Seminal fluid Seroprevalences Serum Shapes Single Nucleotide Polymorphism Specimen Surface Testing Time Vaccine Design Variant Viral Viral Genome Viral Load result Virus Diseases Volatile Fatty Acids base cohort epidemiology study experimental study in vivo infected B cell infection risk keratinocyte laboratory experiment men who have sex with men microbiome 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.

项目摘要摘要卡波西的肉瘤相关疱疹病毒主要由唾液传播，尽管其他路线还描述了包括精液和母乳。 KSHV存在很大的差异不同人群之间的血清阳性。在美国，它不到10％，但在KSHV流行中> 50％撒哈拉以南非洲地区。美国艾滋病-KS的流行是由反复接触驱动的在MSM中，在地方性地区，KSHV是在童年时期获得的。我们正在回应RFA-CA-18- 013以解读KSHV的传输方式。该应用程序的总体目标是了解以分子术语传输KSHV，最终目标是为疫苗设计和确定其他破坏传输的方法。为了实现这一目标，我们将研究三个支柱传染剂的传播性：（i）使用现有的标本中的KSHV菌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和（iii）微生物组的差异，这可能会影响KSHV本身（通过局部病毒载荷测量）和对感染的先天免疫反应。在每种情况下，我们将首先分析自然的人类变异然后探索重要病毒和宿主变体在功能分析中的功能，复制和传输。