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

• 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
• 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

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.

项目概要和摘要 严重发烧伴血小板减少综合征（SFTS）是一种新出现的蜱传疾病，由蜱虫引起 布尼亚病毒，SFTS 病毒 (SFTSV) 由本地长角血蜱传播。 到了东亚，但最近在美国建立了入侵种群，并继续在 亚洲 SFTS 病例发病率不断上升，缺乏具体的治疗策略，病例数较高。 死亡率和蜱传病媒介的全球范围扩张使 SFTS 作为蜱传播的一种公共卫生问题。 SFTSV 与单宿主病毒不同，因为它必须在脊椎动物和 目前，迫切需要阐明蜱内和宿主内的感染动态。 使布尼亚病毒能够在蜱和蜱的不同环境中感染、传播和持续存在 获得这一基础知识对于制定预防的新策略至关重要。 该研究提案是对 NIH RFA-AI-21-046“促进 Bunyavirales 基础科学研究。”总体目标是确定 SFTSV 感染的动态， 蜱载体内的传播和细胞向性，以及蜱到宿主的传播时间线和初始传播 SFTSV 与宿主在皮肤中的相互作用的核心假设是与 H. longicornis 相关的生物因素。 生命周期有利于蜱内SFTSV在蜕皮后传播到唾液腺，从而使 勾选以快速将 SFTSV 传播到它所赖以生存的下一个脊椎动物宿主，同时产生免疫学 蜱取食皮肤部位的特殊微环境将通过追求两个来检验。 具体目标： 1) 描述 SFTSV 感染、传播和跨体育场生存的动态特征 H. longicornis 蜱；以及，2) 定义 SFTSV 和早期宿主的最小蜱至宿主传播时间 皮肤对感染 SFTSV 的蜱的免疫反应的完成将确定感染。 跨多个生命阶段的蜱向量内以及皮肤内SFTSV的动力学和细胞向性 拟议的研究将是第一个集体检查蜱内和宿主内感染的研究。 阐明蜱传布尼亚病毒的基本 H. longicornis-SFTSV-脊椎动物宿主。 相互作用将使未来的工作能够开发出破坏病毒生存的合理干预措施 蜱虫和脊椎动物宿主之间以及蜱虫和脊椎动物宿主之间的传播。