The emergence of Zika virus in Brazil: investigating viral features and host responses to design preventive strategies.

寨卡病毒是一种虫媒病毒，属于黄病毒科属，最初于1947年从乌干达的恒河猴身上分离出来。最常见的症状是皮疹、发烧、关节痛和结膜炎。大多数患者只经历了轻微的一过性疾病，但严重的神经系统并发症已被描述。这种病毒以前在非洲和世界其他地区被描述过，最近在巴西出现了。因此，它是病毒如何在世界各地出现并在新环境中开始传播周期的一个很好的例子。寨卡病毒主要通过伊蚊等蚊子传播。埃及伊蚊。巴西面积很大(850万平方公里)，主要是热带地区。有五个地理区域(北部、东北部、中西部、东南和南部)和五个气候带：赤道、温带、巴西中部热带、东北热带东部和赤道带热带。这些特点有利于Ae的扩散。埃及伊蚊散布在超过3,587个城市的27个巴西联邦单位。除登革热病毒外，其他虫媒病毒目前正在巴西传播。2014年，巴西东北部共发现41例基孔肯雅热输入病例和27例本土病例。最近，巴西卫生部确认了34例寨卡病毒感染病例。确诊病例发生在巴西27个州中的8个州，分布在该国东北部、北部和东南部地区，表明感染广泛。这些暴发的来源和在巴西建立病毒的可能性仍不清楚。寨卡病毒等虫媒病毒有可能引发大规模流行病，在没有任何特定治疗或疫苗的情况下，这些感染可能会极其虚弱。因此，这种新出现的虫媒病毒是一个严重的社会和经济威胁，特别是因为贫困人口对卫生服务的过度需求。寨卡病毒的症状与已经在传播的人类虫媒病毒有关，如登革热和基孔肯雅热。因此，根据临床症状诊断寨卡病毒感染是不可靠的，需要通过实验室诊断来确认。事实上，误解可能会对治疗产生影响，但也会影响对当地人口面临风险的病原体的总体理解。目前寨卡病毒的诊断是基于分子技术，只有少数几个高度专业化的实验室才能获得。该项目建议通过了解个别病例和分析完整的病毒基因组来更好地了解寨卡病毒感染的传播和流行病学，以便将其置于全球背景下。它还将致力于开发可在更广泛的环境中使用的更容易获得的诊断工具，从而支持当地卫生系统。在这一点上，调查寨卡病毒致病过程中涉及的潜在生物学过程以及病毒如何与宿主反应相互作用也至关重要，这可能导致对确诊病例进行更有效的治疗。此外，该项目旨在开发了解和操纵病毒基因组的工具(称为“反向遗传学”)，以更好地了解病毒基因、复制等。这些工具也可以构成未来疫苗的支柱。这个项目的优势是汇集了来自不同研究领域的专家来研究上述问题，目的是显著提高我们对寨卡病毒生物学、对公共卫生的影响以及对这种新兴病毒的研究。这与巴西高度相关，但也与受该病毒影响的其他地区和国家有关。

Zika virus is an arbovirus that belongs to the Flaviviridae family and was initially isolated from rhesus monkeys in Uganda in 1947. The most common reported symptoms are rash, fever, arthralgia, and conjunctivitis. The majority of the patients experiences only a mild and transitory disease, but severe neurologic complications have been described. The virus, previously described in Africa and oher parts of the world, has recently emerged in Brazil. It is thus a good example of how viruses can emerge around the world and start transmission cycles in novel environments. Zika virus is predominantly transmitted by Aedes species mosquitoes such as Ae. aegypti. Brazil is a large (8.5 million km2), predominantly tropical area. There are five geographical regions (North, Northeast, Center-West, Southeast and South) and five climate zones: Equatorial, Temperate, Central Brazil Tropical, Eastern Northeast Tropical and Equatorial Zone Tropical. Such characteristics favor the proliferation of Ae. aegypti mosquitoes that are dispersed around all the 27 Brazilian Federative Units in more than 3,587 cities. Besides dengue viruses, other arboviruses are now circulating in Brazil. In 2014, a total of 41 chikungunya importations and 27 autochthonous cases were detected in northeast Brazil. More recently, 34 cases of ZIKV infection have been confirmed by the Brazilian Ministry of Health. The confirmed cases occurred in eight of the 27 Brazilian states and are distributed in the Northeast, North and Southeast regions of the country, suggesting that the infection is widespread. The source of these outbreaks and the potential for virus establishment in Brazil is still not known. Arboviruses such as Zika have the potential to initiate large scale epidemics, and these infections can be extremely debilitating in absence of any specific treatments or vaccine. Thus, this newly emerged arbovirus represents a serious social and economic threat, especially because of the excessive demand on health services by the poor population. Zika virus symptoms are related to already circulating human arboviruses such as dengue and chikungunya. Thus diagnosis of Zika virus infection on the basis of clinical syndromes is not reliable and needs to be confirmed by laboratory diagnosis. Indeed, misinterpretation may have consequences for treatment but also the general understanding of pathogens local populations are at risk from. Current Zika virus diagnosis is based on molecular techniques only accessible to a few highly specialized laboratories. This project proposes to better understand the spread and epidemiology of Zika virus infection by understanding individual cases and analyse full virus genomes to put them into a global context. It will also aim to develop more easily accessible diagnostic tools that can be used in wider settings thus supporting the local health systems. At this point, it is also crucial to investigate the underlying biological processes involved in Zika virus pathogenesis and how the virus interacts with host responses, which could lead towards more effective treatment of confirmed cases. Moreover this project aims to develop tools to understand and manipulate the viral genome (called "reverse genetics") with view of better understanding viral genes, replication etc. These tools can also form the backbone of future vaccines. The strength of this project is the coming together of experts from different research areas to study the questions outlined above with the aim of significantly improving our understanding of Zika virus biology, impact on public health and study this emerging virus. This is highly relevant to Brazil, but also other regions and countries affected by this virus.