Artificial Ecology Sink as prophylaxis against viral infection

摘要 该项目的总体目标是创建一种基于蛋白质的病毒预防(PVP)，它将提供短期的 (~2-3个月)预防每次静脉输液后的各种病毒感染。此PVP方法 是受到生态源汇理论的启发，该理论认为，景观中的有机体种群 由支持(源)或不支持(汇)其种群的栖息地的频率控制 成长。当一个景观中的下沉栖息地的比例超过 阈值频率。根据这一源汇理论，病毒在体内的传播，从有限的 局部感染(例如，直接接触受感染蚊子唾液的细胞)主要由 低于人体(景观)中汇细胞(汇栖息地)的阈值数量。的核心假说 该项目的目的是在体内引入病毒“汇”细胞，作为预防病毒感染的手段。在……里面 在这个项目中，我提出通过用PVP对宿主细胞进行功能化，将它们转化为人造病毒汇。这个 保护期(2-3个月)虽然比疫苗短得多，但将提供足够的保护 在许多情况下提供保护，如怀孕前三个月的妇女、前往疫区的旅行者、 以及照顾受感染患者的人员。通过重复使用PVP可以实现更长时间的保护 输液或基因疗法。在这个项目中，我将设计针对寨卡病毒的PVP。成功完成这项工作 该项目将为针对许多病原体的新一代预防措施奠定基础，特别是那些 疫苗开发已证明存在困难，例如艾滋病毒和登革热病毒。此外，与传统的 依赖宿主免疫系统产生保护性抗体和/或T细胞的疫苗，通常 在免疫系统较弱的人群中效果较差(非常年长和非常年轻，免疫功能受损 由于艾滋病毒、器官移植等)，PVP将为任何人提供类似级别的保护，无论 由于PVP采用了独特的保护机制，他们的免疫系统健康。

Abstract The overall goal of the project is to create a protein-based viral prophylaxis (PVP) that will provide short-term (~2-3 months) protection against various viral infection following each intravenous infusion. This PVP approach is inspired by the ecological source-sink theory which states that the population of an organism in a landscape is controlled by the frequency of habitats that either support (source) or do not support (sink) its population growth. A population will decline towards extinction when the fraction of sink habitats in a landscape exceeds a threshold frequency. According to this source-sink theory, the spread of viral infection in the body, from a limited local infection (e.g. cells directly contacting the saliva of an infected mosquito), is largely contributed by the below the threshold amount of sink cells (sink habitats) in the body (landscape). The central hypothesis of the project is that the introduction of viral ‘sink’ cells in the body can act as prophylaxis against the viral infection. In this project, I proposed to convert host cells into artificial viral sinks by functionalizing them with PVP. The duration of protection (2-3 months), although much shorter than that of a vaccine, will confer adequate protection in many scenarios, such as women in the 1st trimester of pregnancy, travelers to pandemic areas, and personnel taking care of infected patients. Longer protection from PVP can be achieved through repeated infusion or gene therapy. In this project, I will engineer PVP against Zika virus. Successful completion of this project will lay the foundation of a new generation of prophylaxis against many pathogens, especially those with proven difficulty to vaccine development, such as HIV and dengue virus. In addition, unlike conventional vaccines, which rely on the host immune system to produce the protective antibody and/or T cells, and are often less effective among people with weakened immune system (very old and very young, immune compromised due to HIV, organ transplantation, etc.), PVP will provide similar levels of protection to anyone regardless of the health of their immune system due to the unique protective mechanism employed by PVP.