Abstract
BackgroundTo be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted by Aedes mosquitoes, such as dengue and Zika viruses. The live-attenuated YFV-17D vaccine has been used safely and efficiently on a large scale since the end of World War II. Early studies have shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect Aedes aegypti midgut, but does not disseminate to other tissues.Methodology/Principal findingsHere, we re-visited this issue using a panel of techniques, such as RT-qPCR, Western blot, immunofluorescence and titration assays. We showed that YFV-17D replication was not efficient in Aedes aegypti midgut, as compared to the clinical isolate YFV-Dakar. Viruses that replicated in the midgut failed to disseminate to secondary organs. When injected into the thorax of mosquitoes, viruses succeeded in replicating into midgut-associated tissues, suggesting that, during natural infection, the block for YFV-17D replication occurs at the basal membrane of the midgut.Conclusions/SignificanceThe two barriers associated with Ae. aegypti midgut prevent YFV-17D replication. Our study contributes to our basic understanding of vector–pathogen interactions and may also aid in the development of non-transmissible live virus vaccines.
Highlights
Arboviruses, which are transmitted among vertebrate hosts by blood-feeding arthropod vectors, put billions of people at risk worldwide
The yellow fever vaccine (YFV-17D) is one of the safest and most effective live virus vaccine ever developed. It is used as a platform for engineering vaccines against other health-threatening flaviviruses, such as Japanese encephalitis, West Nile, dengue and Zika viruses
Our data showing that Yellow fever virus (YFV)-17D is unable to disseminate to secondary organs, as compared to a YFV clinical isolate, agree with previous studies
Summary
Arboviruses, which are transmitted among vertebrate hosts by blood-feeding arthropod vectors, put billions of people at risk worldwide. To develop a disseminated infection, virus must escape the midgut into the haemocoel and infect secondary tissues such as the fat body, trachea and the salivary glands [1]. Traditional means of controlling the spread of arbovirus infection include mosquito control and vaccination of susceptible vertebrates. To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have to cross several barriers in the mosquito body, including the midgut infection and escape barriers. Studies have shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect Aedes aegypti midgut, but does not disseminate to other tissues
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