Mechanisms of KSHV Transmission

KSHV 传播机制

• 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
• 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

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 卡波西肉瘤相关疱疹病毒主要通过唾液传播，但也有其他途径 包括精液和母乳也被描述过。KSHV存在着很大的差异 不同人群中的血清阳性率。在美国，这一比例不到10%，但在KSHV地方病中，这一比例为50% 撒哈拉以南非洲地区。而美国的艾滋病-KS疫情是由反复接触推动的 在男男性接触者中，在流行地区，KSHV是在儿童时期感染的。我们正在响应RFA-CA-18- 013破译KSHV是如何传播的。这个应用程序的总体目标是理解 KSHV在分子方面的传播，最终目标是为疫苗设计和 找出其他干扰传播的方法。为了实现这一目标，我们将调查三大支柱 传染性病原体的传播性：(I)使用现有样本的KSHV毒株之间的差异 大的临床队列，(Ii)对KSHV感染的先天免疫反应的差异，以及(Iii) 微生物组的变异可能影响KSHV本身(以当地病毒载量衡量)和 对感染的先天免疫反应。在每一种情况下，我们都将从描绘自然人类变异开始 然后探索重要的病毒和宿主变异体在进入功能检测中的功能， 复制和传播。