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

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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.