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Intra-tick and intra-host infection dynamics of a tick-borne bunyavirus

蜱传布尼亚病毒的蜱内和宿主内感染动态

基本信息

批准号：
10513838
负责人：
Meghan Elizabeth Hermance
金额：
$ 51.82万
依托单位：
UNIVERSITY OF SOUTH ALABAMA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10513838
关键词：
Arboviruses Asia Basic Science Behavioral Biology Bunyavirales Bunyavirus Infections Case Fatality Rates Cells Characteristics Climate Communicable Diseases Cutaneous Data Development Digestion Disease Distal Ecosystem Environment Epidemic Event Far East Feeds Fever Foundations Future Geography Germ Cells Haemaphysalis longicornis Hemocytes Hemorrhage Hour Immune response Immunologics Incidence Infection Infectious Skin Diseases Inflammatory Intervention Kinetics Knowledge Life Life Cycle Stages Midgut Modeling Molting Natural regeneration Nature Organ Orthobunyavirus Physiological Population Process Public Health Publications Publishing Reproduction Request for Applications Research Research Proposals Role Salivary Glands Severe Fever with Thrombocytopenia Syndrome Virus Site Skin Syndrome Testing Thrombocytopenia Tick-Borne Diseases Ticks Time TimeLine Tissues Tropism United States Vertebrate Viruses Viral Load result Virus Virus Diseases Work World Health Organization base feeding in vivo invertebrate host novel novel strategies prevent response tick feeding tick transmission tick-borne tick-borne flavivirus tick-borne virus transmission process treatment strategy vector tick viral transmission virus host interaction

项目摘要

PROJECT SUMMARY & ABSTRACT Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the bunyavirus, SFTS virus (SFTSV). SFTSV is transmitted by the Haemaphysalis longicornis tick, which is native to East Asia but recently established invasive populations in the United States and continues to expand in geographic range. The rising incidence of SFTS cases in Asia, lack of specific treatment strategies, high case fatality rates, and global range expansion of the tick vector make SFTS a public health concern. As a tick-borne virus, SFTSV is unique from single-host viruses because it must replicate and survive in both vertebrate and invertebrate hosts. Currently, there is a critical need to elucidate the intra-tick and intra-host infection dynamics that enable bunyaviruses to infect, disseminate, and persist within the distinct environments of the tick and vertebrate host. Acquiring this fundamental knowledge is paramount to developing novel strategies that prevent SFTSV transmission. This research proposal is in direct response to NIH RFA-AI-21-046, “Promoting Bunyavirales Basic Science Research.” The overall objective is to define the dynamics of SFTSV infection, dissemination, and cell tropism within the tick vector, as well as the tick-to-host transmission timeline and initial SFTSV–host interactions in the skin. The central hypothesis is that biotic factors associated with H. longicornis’ life cycle facilitate intra-tick SFTSV dissemination to the salivary glands after molting, which in turn enables the tick to rapidly transmit SFTSV to the next vertebrate host on which it feeds while creating an immunologically privileged microenvironment at the skin site of tick feeding. The central hypothesis will be tested by pursuing two specific aims: 1) Characterize the dynamics of SFTSV infection, dissemination, and transstadial survival within H. longicornis ticks; and, 2) Define the minimum tick-to-host transmission time of SFTSV and the early host cutaneous immune response to SFTSV-infected tick feeding. Completion of these aims will define the infection kinetics and cell tropism of SFTSV within the tick vector across multiple life stages and within the skin of the vertebrate host. The proposed studies will be the first to collectively examine the intra-tick and intra-host infection dynamics of a tick-borne bunyavirus. Elucidating the fundamental H. longicornis–SFTSV–vertebrate host interactions will enable future work towards the development of rational interventions that disrupt virus survival within, and transmission between, the tick and vertebrate host.

项目总结及摘要