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<h1><B>Have you ever heard </br>the mention of arboviruses ?</B></h1>

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<img src="https://static.igem.org/mediawiki/2016/3/3e/Mosquito_Pasteur.png" width="25%"  alt="image"/></img>

 

 

Arboviruses, arthropod-borne viruses, are important global (re)-emerging viruses (more than 40% of emerging infectious diseases are caused by arboviruses). As its name suggests, arboviruses are transmitted by haematophagous arthropods such as mosquitoes or ticks, and most of them are transmitted by mosquitoes (> 100). When an arbovirus infects mammalians hosts like humans, it causes acute diseases associated with different symptoms ranging from high fever to arthralgias, encephalitis, pulmonary distress, or hemorrhagic fevers. Unfortunately, some causes of these symptoms remain unknown. Nowadays, the vector-borne diseases are among the leading causes of morbidity and mortality in humans and animals, making them a major concern for public health. </br></br></br>

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</a>We have to know that arboviruses don’t represent a single family of viruses but several viruses from different families: Flaviviridae (Dengue virus DENV, Zika virus ZIKV, Yellow Fever virus YFV, West Nile virus WNV, etc), Togaviridae (Chikungunya virus CHIKV, Ross River virus RRV, etc), Bunyaviridae (Rift Valley virus RVV, etc), that’s why specific treatments or vaccines need to be adapted for each family (See <a href="#">IDENTITY CARDS</a> section). </br></br>

By infecting more than 400 million people per year, dengue virus (DENV) is the most important arbovirus. In recent decades, the global incidence of dengue has risen sharply and the transmission has increased in urban and suburban areas. More recently, Zika virus has been on the news : outbreaks occurred in French Polynesia (2013) and Brazil (2016), causing serious neurological complications such as Guillain-Barré syndrome and microcephaly. </br></br>

One of the particularity of the arboviruses is that they infect two kinds of host : a mammalian host that ensure the maintainance and the amplification of the virus, and an arthropod vector (mosquitoes) that ensure its dissemination. In fact, arboviruses originally circulate in a sylvatic cycle in which the virus is transmitted between non-human primates by zoophilic mosquitoes. During its repeated intrusions into forests (hunting, deforestation…), men are accidentally contaminated by contact with anthropo-zoophilic vectors. Then, anthropophilic vectors ensure the dissemination of arboviruses between humans in urban areas, during the urban cycle. </br></br>

<center><img src="https://static.igem.org/mediawiki/2016/d/d8/Cycle_sylvatic_Pasteur_copie.png" alt="" width="100%" /></img></center></br></br></br>

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The lifetime of a mosquito is about 50 days. Its lifestyle changes from the aquatic mode to the terrestrial mode and is divided into 4 stages: egg, larvae, pupae, adult. The mean duration of this developmental cycle is comprised between 8 and 12 days. </br></br>

 

 

Second, when water covers completely the eggs, larvae emerge. Often called “wigglers”, larvae are active in water, where respiration occurs thanks to a siphon on the 8th segment of the abdomen of the larvae. Hung upside-down, larvae eat organic matter such as algae, microscopic organisms in order to ensure its development to the third stage: the pupae.  </br></br>

Instead of larval stage, pupae are not active and do not feed. A pair of respiratory trumpets allows pupae to live 2-3 days. </br></br>

Then, an adult mosquito emerges and flies away. Male and female adult mosquitoes are physically distinguishable thanks to a very bushy antennae of the male, allowing it to sense females. While males feed on nectar and sources of sugar, only females are haematophagous because they need supplemental proteins to develop eggs. During blood-feeding, adult female mosquitoes bite people and animals and pumps blood. We don’t feel the bite of the mosquito because of the anesthetic agents injected through its saliva (that contains anticoagulants, anti-inflammatory molecules, and in some cases arboviruses). That’s why a lot of pathogens are transmitted by mosquitoes. </br></br>

<center><img src="https://static.igem.org/mediawiki/2016/4/49/Cycle_de_vie_des_moustiques_Pasteur.png" alt="" width="90%"/></img></center></br></br></br>

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Fortunately, all mosquitoes are not able to transmit arboviruses! The competence of a mosquito is the ability of a vector to be infected by and to transmit a pathogen in natural conditions. For example, competent vectors of malaria are Anopheles mosquitoes. Competent vectors for DENV, CHIKV, ZIKV, YFV, RRV, etc are Aedes aegypti and Aedes albopictus mosquitoes. </br></br>

<center><img src="https://static.igem.org/mediawiki/2016/1/19/Aedes.png" width="90%"  alt="image"/></img></center></br>

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An arbovirus-related outbreak arises when the virus is introduced into a permissive environment where coexists anthropophilic competent vectors and susceptible human population. The mosquito becomes infected when taking a blood meal from a vertebrate host in a phase of viremia. In the mosquito, the virus can replicate itself, transit across various anatomical barriers of the mosquito and join salivary glands. Once in the saliva, the virus is transmitted to the host during blood-feeding. The period between infection of the mosquito by a human and infection of a human by the same mosquito changes according to the temperature. At 20°C, this extrinsic incubation period (EIP) is about 2 weeks but at 35°C, in endemic areas, this EIP can be achieved in less than one week! </br></br>

Since only yellow fever is prevented by vaccination, the single efficient method to fight against arboviruses is vector control. Several methods exist but the most common is insecticide spraying (particularly pyrethroids and organophosphates). Unfortunately, mosquitoes become more and more resistant and more and more classes of insecticides are developed, increasing multiresistances and high environmental impact. Moreover, since we are unable to maintain effective control of mosquito populations, the fact that resistance contributes to the re-emergence of arboviruses cannot be excluded. That’s why insecticide resistance is now regarded by the WHO as a major obstacle to the control of diseases transmitted by mosquitoes. Many organizations are created and act together. For example, in accordance with the Research and Training Program on Tropical Diseases (TDR), supported by WHO, the Department of Neglected Tropical Diseases (NTDs) and the WIN network met for the first time. WIN network is comprised of fifteen international institutions recognized for research on vectors to counter the resistance to insecticides globally. Additionally, the IRD, CNRS and the Institut Pasteur of French Guiana are highly mobilized at the French level. Concerning France, insecticides are sprayed when human infected cases are identified and where competent mosquitoes are present. Considering asymptomatic carriers, symptomatic carriers who think having flu, and physicians who don’t report identified cases, the majority of disease importations are not detected. Moreover, when identified cases are reported, insecticide spraying occursthere, ignoring the possibility of mobility of infected people or infected mosquitoes. It seems obvious that it could be better to anticipate disease importations and outbreaks occurrences by acting before infected cases identification happens. Finally, competent vectors repartition all over the world is well known but infected vectors repartition is not. By mapping the infected vectors’ repartition, we could perform a more rational use of insecticides and focus our efforts on concerned regions. </br></br>

In this context, our Mos(kit)O project consists in the development of the infected mosquitoes mapping, this indispensable tool that vector control is lacking. Let us present to you our Mos(kit)O project in <a href="https://2016.igem.org/Team:Pasteur_Paris/Overview">OVERVIEW</a> section!