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KSHV infection of human tonsillar B cells

KSHV 感染人扁桃体 B 细胞

基本信息

批准号：
8595175
负责人：
Dean H Kedes
金额：
$ 38.5万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8595175
关键词：
Acquired Immunodeficiency Syndrome Address Affect Antibodies Apoptosis B-Cell Activation B-Lymphocyte Subsets B-Lymphocytes Biology Blood Circulation Cancer Etiology Cell Survival Cell physiology Cells Cellular Morphology Characteristics Coupled Data Disease Distal Endothelial Cells Epidemiology Epigenetic Process Exposure to Flow Cytometry Foundations Genes Genetic Transcription Goals Herpesviridae Herpesviridae Infections Human Human Herpesvirus 8 Image Imagery Immune Immunoglobulin M Individual Infection Inflammatory Kaposi Sarcoma Laboratories Light Link Lymphatic Lytic Malignant Neoplasms Measures MicroRNAs Modeling Modification Molecular Profiling Multicentric Angiofollicular Lymphoid Hyperplasia Nature Oral Oral cavity Organ Organ Transplantation Orthologous Gene Pathogenesis Pathologic Patients Pattern Peripheral Persons Phenotype Play Population Predisposition Proteins Reporter Reverse Transcriptase Polymerase Chain Reaction Role Route SECTM1 gene Saliva Site Solid Sorting - Cell Movement Source Staging Testing Tonsil Transcript Transplant Recipients Tropism Viral Viral Genes Viral Proteins Virion Virus Work base cell type cytokine functional outcomes gammaherpesvirus infected B cell intercellular communication latency-associated nuclear antigen latent gene expression latent infection peripheral blood primary effusion lymphoma promoter transmission process tumor tumorigenesis tumorigenic viral detection

项目摘要

DESCRIPTION (provided by applicant): Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8) establishes lifelong infection and is the etiologic agent underlying primary effusion lymphoma, multicentric Castleman's disease, and Kaposi's sarcoma, an endothelial cell-based angiogenic tumor that remains the most prevalent AIDS-associated malignancy worldwide. Although the site for a definitive latent reservoir(s) remains unclear, KSHV can infect B cells in the oral cavity and express a number of viral proteins capable of modulating B cell signaling and survival. Shedding of KSHV in the saliva is frequent in infected individuals and concentrations are often higher than in the peripheral blood. Further, epidemiologic work implicates saliva as a major source for person-to-person viral transmission with infected tonsillar B cells also providing a potential source of spread to distal sites within individuals. In contrast, KSHV-infected B cells in the peripheral circulation are extremely rare in asymptomatic individuals and only slightly less infrequent in patients with early stages of disease. These observations suggest that KSHV may preferentially infect a subset of B cells present in the lymphatic organs of the oral cavity. Our overarching hypothesis is that oral exposure to KSHV leads to selective infection of a specific subset of human tonsillar B cells, effecting phenotypic and functional changes favorable to viral persistence and predictive of pathologic potential. Very little is known about the critical identity and character of KSHV-susceptible B cells in the oral cavity, the nature of the infection, the mechanism underlying differential tropism, or the characteristics of KSHV-induced changes in B cell phenotype and function. We propose to answer these questions. It is our long-term goal to causally link these changes with the expression of specific viral genes and identify those alterations potentially responsible for initiating and sustaining KSHV pathogenesis.)

描述（由申请人提供）：卡波西肉瘤相关疱疹病毒（KSHV），也被称为人类疱疹病毒8 (HHV8)，建立终身感染，是原发性积液性淋巴瘤、多中心Castleman病和卡波西肉瘤的病因，卡波西肉瘤是一种基于内皮细胞的血管生成肿瘤，仍然是世界上最普遍的艾滋病相关恶性肿瘤。虽然最终的潜伏库的位置尚不清楚，但KSHV可以感染口腔中的B细胞并表达一些能够调节B细胞信号传导和存活的病毒蛋白。唾液中KSHV的脱落在感染者中很常见，其浓度通常高于外周血。此外，流行病学研究表明，唾液是感染扁桃体B细胞的人与人之间病毒传播的主要来源，也是个体远端传播的潜在来源。相比之下，外周循环中感染kshv的B细胞极为罕见