There are over a hundred mosquito-borne diseases, including dengue – which affects over 50 million people each year – and chikungunya. These are arboviruses, in other words viruses that are transmitted between vertebrates via a bite from a hematophagous vector. Scientists at the Institut Pasteur have developed a mosquito that can recognize the dengue and chikungunya viruses and limit viral infection. This paves the way for an alternative arbovirus control strategy based on genetically modified mosquito vectors.
Mosquitoes are the main vectors of several pathogens responsible for human diseases, including malaria, dengue, chikungunya and yellow fever. Every year, 600,000 people die from malaria and 30,000 from dengue – and mosquito-borne diseases also represent a huge economic burden for those countries affected (see our report on The Geopolitics of the Mosquito).
Female mosquitoes that feed on humans can ingest viruses circulating in the blood they absorb. If the mosquito is a "competent" vector, the virus can overcome all the various obstacles (anatomical barriers and immune responses of the mosquito) and be transmitted via a mosquito bite.
Making use of the properties of microRNAs
"Once the mosquito has been infected, it remains infected throughout its lifetime," explains Pei-Shi Yen, a scientist in the Arboviruses and Insect Vectors Unit, directed by Anna-Bella Failloux at the Institut Pasteur. "But when the mosquito is infected, it reacts by triggering a number of antiviral responses to limit the infection," he continues. For example, it may synthesize microRNAs (or miRNAs) to counter viral replication in host cells. These miRNAs are typically involved in regulating gene expression.
Given the limited efficacy of methods for controlling mosquito populations, finding alternative strategies has become a matter of urgency. "We made use of the properties of miRNAs to develop a mosquito that can limit viral infection," continues the scientist. "We genetically modified the mosquito by integrating antiviral miRNAs into its genome that are capable of recognizing the dengue and chikungunya viruses."
The synthetic miRNAs match up with viral RNAs containing a homologous sequence and cause their degradation. "We demonstrated that these genetically modified mosquitoes were less effective in transmitting the virus: we observed a 77.33% reduction in efficacy for chikungunya transmission and a 100% reduction for the dengue virus," concludes Pei-Shi Yen. This research therefore paves the way for an alternative arbovirus control strategy based on genetically modified mosquito vectors.
Synthetic miRNAs induce dual arboviral-resistance phenotypes in the vector mosquito Aedes aegypti, Communications Biology, February 8, 2018.
YEN Pei-Shi, JAMES Anthony, LI Jian-Chiuan, CHEN Chun-Hong, FAILLOUX Anna-Bella.
YEN Pei-Shi1, JAMES Anthony2, LI Jian-Chiuan3, CHEN Chun-Hong3, FAILLOUX Anna-Bella1.
1. Institut Pasteur, Department of Virology, Unit of Arboviruses and Insect Vectors, Paris 75015, France.
2. Departments of Microbiology & Molecular Genetics and Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.
3. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Miaoli 35053, Taiwan.