Immunology, molecular biology and control of flaviviruses (Dengue and Zika)

免疫学、分子生物学和黄病毒（登革热和寨卡病毒）的控制

• 批准号: 1923696
• 金额: --
• 依托单位: London School of Hygiene & Tropical Medicine
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1923696
• 关键词: Immunology; molecular; biology; control; flaviviruses

The flaviviruses Dengue and Zika are endemic to much of the tropical and sub-tropical areas of the world. Spread by Aedes mosquitos, one estimate indicates 390 million dengue infections per year, of which 96 million manifest clinically (with any severity of disease). Another study, of the prevalence of dengue, estimates that 3.9 billion people, in 128 countries, are at risk of infection with dengue viruses. Although Zika virus was first identified in the 1950s it was an outbreak in 2015 in South America which brought it to global attention, during this outbreak there was a marked increase in cases of children born with birth defects. The efficiency of Dengue disease transmission can be seen in places such as Singapore, where very low numbers of these mosquitos can be found (Aedes premises index of less than 1% and virtually no infected mosquitos identified) and yet incidence rates are high (typically more than 200 cases notified per year per 100,000 residents) and in 2013 there were more than 23,000 hospitalizations (for a population of 5.5 million).Despite Dengue virus being one of the most studied viruses, some critical components of the epidemiology dynamics are unknown. For example; the mosquito typically only flies 150m in its life time of two weeks (and two feeding periods) and dengue infected patients are typically only contagious to the mosquito for 3 to 6 days (during the fever stage). Extensive recent research has concentrated on explaining mosquito numbers in relation to weather variables and correlating this to disease incidence, but further work integrating this knowledge with viral molecular epidemiology is likely to reveal more precise details of how the disease spreads from person to person.Next-generation sequencing technologies can allow phylogenetic analysis of viral outbreaks, can reveal the path of the outbreak and additionally can detect mutations that may be associated with new disease phenotypes or affect molecular diagnostics. These can be used to therefore infer transmission dynamics. This project will utilize a comprehensively monitored cohort from Vietnam to follow real time dengue outbreaks, household clusters of cases and obtain blood samples that will permit molecular typing, together with serological data. Taken together, this data will enable mathematical model testing and refinement; while also initiating a field site that could later be used for interventions.I will initially be focussing on developing and using molecular detection techniques to diagnose and sequence the virus. Data generated by this will then be used to infer routes of transmission as well as how the virus responds to immunological pressures.

登革热和寨卡是世界上许多热带和亚热带地区的地方病。登革热由伊蚊传播，一项估计表明每年有3.9亿人感染登革热，其中9600万人表现为临床症状（任何疾病严重程度）。另一项关于登革热流行情况的研究估计，128个国家的39亿人面临感染登革热病毒的风险。虽然寨卡病毒在20世纪50年代首次被发现，但2015年在南美洲爆发，引起了全球的关注，在这次爆发期间，出生缺陷儿童的病例显着增加。登革热传播的效率可以在新加坡等地看到，在那里可以找到非常低数量的这些蚊子（伊蚊活动场所指数低于1%，几乎没有发现受感染的蚊子），但发病率很高（通常每10万居民每年通报200多起案件），2013年有23多起，尽管登革热病毒是研究最多的病毒之一，但流行病学动态的一些关键组成部分是未知的。例如：蚊子通常在其两周的寿命（和两个进食期）中仅飞行150米，并且登革热感染的患者通常仅对蚊子具有3至6天的传染性（在发烧阶段期间）。最近的大量研究集中在解释蚊子数量与天气变量的关系，并将其与疾病发生率相关联，但将这一知识与病毒分子流行病学相结合的进一步工作可能会揭示疾病如何在人与人之间传播的更精确细节。下一代测序技术可以对病毒爆发进行系统发育分析，可以揭示疾病爆发的路径，还可以检测可能与新疾病表型相关或影响分子诊断的突变。因此，这些可以用于推断传输动态。该项目将利用来自越南的一个全面监测的队列，跟踪登革热疫情的真实的时间、家庭聚集病例，并获取血液样本，以便进行分子分型，同时提供血清学数据。总的来说，这些数据将使数学模型的测试和完善，同时也启动了一个现场，可用于以后的干预。我将首先集中在开发和使用分子检测技术来诊断和测序病毒。由此产生的数据将用于推断传播途径以及病毒如何对免疫压力作出反应。