The growing expansion of mosquito vectors has made mosquito-borne arboviral diseases a global threat to public health, and the lack of licensed vaccines and treatments highlight the urgent need for efficient mosquito vector control. Compared to genetically modified control strategies, the intracellular bacterium Wolbachia, endowing a pathogen-blocking phenotype, is considered an environmentally friendly strategy to replace the target population for controlling arboviral diseases. However, the incomplete knowledge regarding the pathogen-blocking mechanism weakens the reliability of a Wolbachia-based population replacement strategy. Wolbachia infections are also vulnerable to environmental factors, temperature, and host diet, affecting their densities in mosquitoes and thus the virus-blocking phenotype. Here, we review the properties of the Wolbachia strategy as an approach to control mosquito populations in comparison with genetically modified control methods. Both strategies tend to limit arbovirus infections but increase the risk of selecting arbovirus escape mutants, rendering these strategies less reliable.

Mosquito-borne arboviruses are responsible for recent dengue, chikungunya, and Zika pandemics. The yellow-fever mosquito,Aedes aegypti, plays an important role in the transmission of all three viruses. We developed a miRNA-based approach that results in a dual resistance phenotype in mosquitoes to dengue serotype 3 (DENV-3) and chikungunya (CHIKV) viruses. The target viruses are from two distinct arboviral families and the antiviral mechanism is designed to function through the endogenous miRNA pathway in infected mosquitoes. Challenge experiments showed reductions in viral transmission efficiency of transgenic mosquitoes. Several components of mosquito fitness were examined, and transgenic mosquitoes with thePUbpromoter showed minor fitness costs at all developing stages. Further development of these strains with gene editing tools could make them candidates for releases in population replacement strategies for sustainable control of multiple arbovirus diseases.

Among the strategies targeting vector control, the exploitation of the endosymbiont Wolbachia to produce sterile males and/or invasive females with reduced vector competence seems to be promising. A new Aedes albopictus transinfection (ARwP-M) was generated by introducing wMel Wolbachia in the ARwP line which had been established previously by replacing wAlbA and wAlbB Wolbachia with the wPip strain. Various infection and fitness parameters were studied by comparing ARwP-M, ARwP and wild-type (S_ANG population) Ae. albopictus sharing the same genetic background. Moreover, the vector competence of ARwP-M related to chikungunya, dengue and zika viruses was evaluated in comparison with ARwP. ARwP-M showed a 100% rate of maternal inheritance of wMel and wPip Wolbachia. Survival, female fecundity and egg fertility did not show to differ between the three Ae. albopictus lines. Crosses between ARwP-M males and S_ANG females were fully unfertile regardless of male age while egg hatch in reverse crosses increased from 0 to about 17% with S_ANG males aging from 3 to 17 days. When competing with S_ANG males for S_ANG females, ARwP-M males induced a level of sterility significantly higher than that expected for an equal mating competitiveness (mean Fried index of 1.71 instead of 1). The overall Wolbachia density in ARwP-M females was about 15 fold higher than in ARwP, mostly due to the wMel infection. This feature corresponded to a strongly reduced vector competence for chikungunya and dengue viruses (in both cases, 5 and 0% rates of transmission at 14 and 21 days post infection) with respect to ARwP females. Results regarding Zika virus did not highlight significant differences between ARwP-M and ARwP. However, none of the tested ARwP-M females was capable at transmitting ZIKV. These findings are expected to promote the exploitation of Wolbachia to suppress the wild-type Ae. albopictus populations. Aedes albopictus is one of the major human disease vectors and, despite substantial control efforts, it is rapidly spreading worldwide and increasing its epidemiological role. Thus, innovative approaches to fight this mosquito are urgently needed. Among the available control strategies, the exploitation of the endosymbiotic bacterium Wolbachia seems to be promising. In nature, the infection by Wolbachia is generally not detrimental, instead, it causes a series of modifications in host physiology promoting the spread of the infection in uninfected populations. Herein, we report on the artificial transinfection of specific Wolbachia strains in Ae. albopictus to replace its native Wolbachia infection type. This manipulation aimed at exploiting the expected modifications in the reproductive biology and vector competence of the species to contribute to reduce its epidemiological role. Specifically, we found that the new double Wolbachia infection did not affect Ae. albopictus fitness. The males belonging to the manipulated line, ARwP-M, induced full egg infertility in the wild-type females they mate with and showed increased male mating competitiveness. Remarkably, the ARwP-M females demonstrated significantly reduced competence for chikungunya and dengue viruses while both tested Ae. albopictus lines showed a very low susceptibility for Zika virus. These findings may encourage the use of ARwP-M Ae. albopictus as a highly efficient and safe biocide to suppress the wild-type populations.

Historically endemic to Sub-Saharan Africa and South America, yellow fever is absent from the Asia-Pacific region. Yellow fever virus (YFV) is mainly transmitted by the anthropophilic Aedes mosquitoes whose distribution encompasses a large belt of tropical and sub tropical regions. Increasing exchanges between Africa and Asia have caused imported YFV incidents in non-endemic areas, which are threatening Asia with a new viral emergence. Here, using experimental infections of field-collected mosquitoes, we show that Asian-Pacific Aedes mosquitoes are competent vectors for YFV. We observe that Aedes aegypti populations from Singapore, Taiwan, Thailand, and New Caledonia are capable of transmitting YFV 14 days after oral infections, with a number of viral particles excreted from saliva reaching up to 23,000 viral particles. These findings represent the most comprehensive assessment of vector competence and show that Ae. aegypti mosquitoes from the Asia-Pacific region are highly competent to YFV, corroborating that vector populations are seemingly not a brake to the emergence of yellow fever in the region.

Arboviral diseases such as chikungunya, dengue, and Zika viruses have been threatening the European countries since the introduction in 1979 of the major vectorAedes albopictus. In 2017, more than three hundred of CHIKV autochthonous cases were reported in Italy, highlighting the urgent need for a risk assessment of arboviral diseases in European countries. In this study, the vector competence for three major arboviruses were analyzed in eightAe.albopictuspopulations from Europe. Here we show that Southern EuropeanAe.albopictuswere susceptible to CHIKV, DENV-1 and ZIKV with the highest vector competence for CHIKV. Based on vector competence data and vector distribution, a prediction risk map for CHIKV was generated stressing the fear of CHIKV and to a lesser extent, of other arboviruses for Europe, calling us for new public health strategies.

This last decade has seen a resurgence of yellow fever (YF) in historical endemic regions and repeated attempts of YF introduction in YF‐free countries such as the Asia‐Pacific region and the Caribbean. Infected travellers are the main entry routes in these regions where competent mosquito vectors proliferate in appropriate environmental conditions. With the discovery of the 17D vaccine, it was thought that YF would be eradicated. Unfortunately, it was not the case and, contrary to dengue, chikungunya and Zika, factors that cotribute to YF transmission remain under investigation. Today, all the signals are red and it is very likely that YF will be the next pandemic in the YF‐free regions where millions of people are immunologically naïve. Unlike COVID‐19, YF is associated with a high case‐fatality rate and a high number of deaths are expected. This review gives an overview of global YF situation, including the non‐endemic Asia‐Pacific region and the Caribbean where Aedes aegypti is abundantly distributed, and also proposes different hypotheses on why YF outbreaks have not yet occurred despite high records of travellers importing YF into these regions and what role Aedes mosquitoes play in the emergence of urban YF.