The mosquito Temples of the Egyptians is the main vector of dengue fever, Zika virus infection, chikungunya and yellow fever. © Adobe Stock
Aedes mosquitoes are the main vectors of the dengue virus and other arboviruses, including the Zika virus, for which we currently have neither a vaccine nor an antiviral treatment. Understanding the factors that influence the transmission of arboviruses from mosquitoes to humans is therefore a priority because it could guide the implementation of public health measures that can limit or even prevent epidemics. In a new study, a team of researchers from Inserm, CNRS and the University of Strasbourg at the Institute of Molecular and Cellular Biology, in collaboration with the Federal University of Minas Gerais in Brazil, described all the viruses (the virome) present in 800 mosquitoes collected in 6 countries, on 4 continents. Scientists show that of the 12 viruses identified, two of them do not infect humans but increase the transmission potential of dengue and Zika viruses. The mechanism involved reveals the existence of a new cellular factor hijacked by arboviruses in mosquitoes. These results are published in the journal Nature Microbiology.
Dengue fever is the fastest growing mosquito-borne viral infectious disease in the world, currently causing 400 million new infections each year. This increase in cases of dengue, but also other diseases caused by viruses transmitted by mosquitoes (“arthropod-borne viruses” or arboviruses), such as Chikungunya and Zika, reflects the geographical expansion of the main mosquito vectors, Temples of the Egyptians et A. albopictusin particular due to the globalization of trade and climate change.
Virological surveillance of adult Aedes mosquitoes by metagenomic analysis[1] can lead to early identification of circulating arboviruses and thus contribute to improving public health measures. In addition to arboviruses, these surveillance methods have identified a large number of insect-specific viruses in Aedes mosquitoes. Although they do not infect mammals, these viruses are likely to have an impact on the transmission dynamics of arboviruses to humans.
It is in this context that the work of a team of scientists from Inserm, CNRS and the University of Strasbourg fits in, which has undertaken the characterization of the global virome of Aedes mosquitoes on a planetary scale. .
Using a high-throughput RNA sequencing technique[2], coupled with a bioinformatics analysis using a method developed in their laboratory, the researchers carried out an inventory of the viruses present in Aedes mosquitoes throughout the world. They relied on a network of collaborators, most of them participating in the European consortium ZIKAlliance[3], to collect more than 800 mosquitoes from 12 different sites in 6 countries on 4 continents. This allowed them to identify 12 circulating viruses present in these mosquitoes, 5 of which had not yet been described.
Two of these 12 viruses, PCLV (Phasi Charoen-like virus) and HTV (Humaita Tubiacanga virus)[4], attracted the attention of researchers due in particular to their high prevalence (they were indeed present in more than half of the samples). HTV and PCLV were not or only slightly present in samples from Africa, where there are few dengue cases, compared to Asia or South America, where there are many.
To find out if these two viruses could have an impact on dengue transmission, the scientists looked at a small town in southeastern Brazil, Caratinga, where dengue is endemic and for which they had an archived collection. of RNAs from more than 500 mosquitoes collected at this location over a year. This analysis of samples collected in the field revealed an interaction of the two viruses HTV and PCLV with the dengue virus: mosquitoes infected with the HTV and PCLV viruses had a three times higher probability of also being infected with the dengue virus. the dengue.
The scientists then confirmed this observation in the controlled environment of the Strasbourg insectarium, showing that the introduction of HTV and PCLV viruses into laboratory mosquitoes increased the replication of dengue (DENV) and Zika viruses. (ZIKV). A higher level of these viruses shortens the extrinsic incubation period, ie the time it takes for infected mosquitoes to become infectious. Using mathematical modelling, the researchers suggest that this higher infectious capacity could increase the risk of dengue and Zika transmission by five times when HTV and PCLV are present.
All of these results raise the question of the mechanism by which HTV and PCLV affect the replication of the DENV and ZIKV viruses. Researchers have tried to find some explanations.
By studying gene expression in dengue-infected mosquitoes in the absence or presence of HTV and PCLV, scientists discovered the important role of histones (proteins that bind to DNA for compact and form chromatin), especially histone H4. Their results show that the dengue virus uses histone H4 to multiply in mosquitoes. HTV and PCLV, by a mechanism which remains to be determined, maintain the expression of histone H4 in infected mosquitoes, thus favoring this multiplication of the dengue virus.
“A better knowledge of the molecular mechanisms that govern the interaction between these three viruses seems essential for the continuation of our research. Understanding what favors the transmission of the Zika and dengue viruses could make it possible to propose more effective strategies to reduce the transmission of the virus to humans, and to limit or even prevent epidemics”, concludes João Marques, newly recruited Inserm research director and last author of the study.
[1] Method for studying the genetic content of samples from complex environments taken from nature, here samples taken from mosquitoes.
[2] Sequencing of a very large number of different molecules within the same sample
[3] ZIKAlliance is a multinational and multidisciplinary research consortium made up of 54 partners worldwide and coordinated by Inserm. ZIKAlliance is funded by the European Union’s Horizon 2020 research and innovation program.
[4] Virus that was discovered by this same team as part of previous work.
