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.

项目总结与摘要 严重发热伴血小板减少综合征(SFTS)是一种新出现的硬体传播疾病，由 布尼亚病毒，SFTS病毒(SFTSV)。SFTSV是由本地的长角血蜱传播的 到东亚，但最近在美国建立了入侵种群，并继续在 地理范围。亚洲SFTS病例发病率上升，缺乏专门的治疗策略，病例较高 病死率和滴虫媒介的全球范围扩大使SFTS成为一个公共卫生问题。作为扁虱传播的 作为一种病毒，SFTSV不同于单宿主病毒，因为它必须在脊椎动物和 无脊椎动物宿主。目前，迫切需要阐明硬体内和宿主内感染的动力学。 使本雅氏病毒能够感染、传播并持续存在于扁虱的不同环境中 脊椎动物宿主。获得这一基本知识对于开发新的战略至关重要，这种战略可以防止 SFTSV传输。这项研究建议是对NIH RFA-AI-21-046的直接回应， 布尼亚维拉莱斯基础科学研究中心。总体目标是确定SFTSV感染的动力学， 媒介内的传播和细胞嗜性，以及从蚊子到宿主的传播时间线和初始 SFTSV-在皮肤中承载交互。中心假说是与长角毛虫有关的生物因素 生命周期促进扁虱内SFTSV在蜕皮后传播到唾液腺，这反过来又使 勾选以将SFTSV快速传播给它赖以生存的下一个脊椎动物宿主，同时在免疫上创造一个 取食扁虱皮肤部位的特殊微环境。核心假说将通过追求两个 具体目标：1)描述流行性出血热病毒感染、传播和经生殖道存活的动态 以及，2)定义SFTSV和早期寄主的最短寄生时间 感染猪瘟病毒的硬蜱饲养引起的皮肤免疫反应。完成这些目标将定义感染 森林口蹄疫病毒跨多个生命阶段和皮肤内的动态和细胞嗜性 脊椎动物宿主。这项拟议的研究将是第一次集体检查扁虱内感染和宿主内感染。 壁虱传播的布尼亚病毒的动态。长角华支睾吸虫脊椎动物基本寄主的研究 相互作用将使未来的工作朝着开发干扰病毒生存的合理干预措施的方向发展 在硬体动物和脊椎动物宿主内部和之间传播。