Partial masculinization of Aedes aegypti females by conditional expression of Nix.

Background: Aedes aegypti, the main vector of dengue, yellow fever, and other arboviruses thrives in tropical and subtropical areas around the globe putting half of the world's population at risk. Despite aggressive efforts to control the transmission of those viruses, an unacceptable number of cases occur every year, emphasizing the need to develop new control strategies. Proposals for vector control focused on population suppression could offer a feasible alternative method to reduce disease transmission. The induction of extreme male-biased sex ratios has been hypothesized to be able to suppress or collapse a population, with previous experiments showing that stable expression of the male determining factor Nix in A. aegypti is sufficient to convert females into fertile males. Methodology/Principal findings: Here, we report on the conditional expression of Nix in transgenic A. aegypti under the control of the tetracycline-dependent (Tet-off) system, with the goal of establishing repressible sex distortion. A masculinization phenotype was observed in three of the seven transgenic lines with females exhibiting male-like long maxillary palps and most importantly, the masculinized females were unable to blood feed. Doxycycline treatment of the transgenic lines only partially restored the normal phenotype from the masculinized transgenic lines, while RT-qPCR analysis of early embryos or adults showed no correlation between the level of masculinization and ectopic Nix expression. Conclusions/Significance: While the conditional expression of Nix produced intersex phenotypes, the level of expression was insufficient to program full conversion. Modifications that increase both the level of activation (no tet) and the level of repression (with tet) will be necessary, as such this study represents one step forward in the development of genetic strategies to control vector-borne diseases via sex ratio distortion. Author summary: Morbidity and mortality from vector-borne diseases are an increasing public health problem. Approaches to reduce mosquito abundance to control pathogen transmission, known as population suppression, have been under development in an attempt to decrease the burden imposed by such diseases. One proposed strategy to collapse vector populations relies on skewing the sex ratio equilibrium to compromise fertility. Based on that, this research demonstrates the conditional expression of the male determining factor of the mosquito Ae. aegypti with the goal of establishing repressible sex distortion. Although full conversion of females into males was not achieved, a masculinization phenotype was observed in some transgenic lines, providing the foundation for the development of a new category of genetic vector control strategy via sex ratio distortion. [ABSTRACT FROM AUTHOR]