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Arthropod exosomes mediate vector-pathogen interactions

节肢动物外泌体介导载体-病原体相互作用

基本信息

批准号：
10454410
负责人：
Hameeda Sultana
金额：
$ 36.5万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
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：
2019-08-19 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10454410
关键词：
Address Affect Arbovirus Infections Area Arthropod Vectors Arthropods Biochemical Biological Biological Assay Biology Black-legged Tick Blood Caliber Cell Line Cells Data Detection Development Disease Electron Microscopy Electrons Endothelial Cells Enzymes Flavivirus Flavivirus Infections Gel Genes Goals Human Immune response Immunization In Vitro Infection Langat virus Lead Life Cycle Stages Mammalian Cell Mediating Mediator of activation protein Medical Microscopic Migration Assay Modeling Molecular Mus Paper Production Proteins Proteomics Publishing RNA RNA Interference Research Role Salivary Gland Tissue Salivary Glands Secure Signal Transduction Skin Sphingomyelinase Techniques Testing Tick-Borne Encephalitis Virus Ticks Time Two-Dimensional Gel Electrophoresis Validation Vector-transmitted infectious disease Vesicle Viral Viral Proteins Viral load measurement Virulent Virus Virus Diseases arthropod-borne cell type evaluation/testing exosome extracellular feeding gel electrophoresis inhibitor insight keratinocyte knock-down microvesicles mouse model novel pathogen recruit therapeutic evaluation tick feeding tick saliva tick transmission tick-borne tick-borne flavivirus transmission process transmission-blocking vaccine vector vector tick vector transmission vector vaccine viral RNA viral transmission

项目摘要

Project Summary/Abstract Ticks transmit several pathogens including flaviviruses that cause diseases in humans. The molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we provide strong preliminary data that show for the first time that a cell line from medically important arthropods, such as ticks, secretes exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. We noted that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses tick exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo- EM analysis revealed presence of tick exosomes with the size range of 30 to 200 nm in diameter. Detection of both positive and negative LGTV RNA strands and proteins such as Envelope (E) and Non- structural 1 (NS1) inside arthropod exosomes confirmed that tick exosomes contain viral RNA and proteins. Viral RNA and proteins in exosomes derived from tick and mammalian cells were secured, highly infectious and replicative in all tested evaluations. Furthermore, treatment of tick cells with GW4869, a selective inhibitor that blocks exosome production affected LGTV loads and transmission from arthropod to human cells. 1-D gel electrophoresis further revealed presence of several arthropod exosome-enriched tick molecules. These preliminary results form the strong basis for the proposal to characterize role of arthropod exosomes in tick-LGTV interactions. Several approaches that delineate molecular signaling and identification of arthropod exosomal proteins in tick-LGTV interactions are proposed. We hypothesize that tick exosomal-enriched proteins could be considered as ideal candidates for the development of anti- vector vaccines. The proposed aims provide important insights to define molecular basis of the relationship between tick exosomes and pathogens. This is a transformative and a novel study that not only provides information on the role of arthropod exosomes in vector-pathogen interactions but also lead to the development of better strategies to treat or control transmission of pathogens from this and perhaps other vectors of medical importance.

项目总结/文摘