Using Wolbachia infected mosquitos to combat arboviral transmission: from molecular mechanisms to global application

The global disease burden inflicted by arboviruses such as dengue, Zika, and chikungunya viruses represents a pressing public health crisis. These mosquito-borne diseases co-circulate in the common Aedes aegypti vector, leading to co-morbidities and mortalities, often in low-income countries. Despite the prevalence of arboviruses worldwide, no reliable antivirals or vaccines are currently available. Furthermore, existing strategies for vector biocontrol, such as insecticide dissemination, have resulted in resistance development in mosquitos and can lead to toxic bioaccumulation within ecosystems. Wolbachia is an obligate intracellular bacterium that has co-evolved over 200 million ears to live in endosymbiosis with 60-70% of insects. Wolbachia transmission between insects is exclusively limited to vertical transmission between females and their offspring. As a result, Wolbachia has evolved mechanisms to promote its own transmission and persistence within insect populations. These mechanisms include preventing live births between Wolbachia-infected males and uninfected females. Moreover, Wolbachia alters the insect immune system and lipid homeostasis to protect against invasion from other pathogens, rendering mosquitos remarkably resistant to arboviral infection. Recently, these mechanisms have been exploited as novel techniques to combat arboviral transmission. By releasing Wolbachia-infected mosquitos to areas afflicted by arboviral outbreaks, researchers have hoped to curtail new infections by rendering A. aegypti an ineffective vector (Fig. 1). This article will first provide an in-depth review of the molecular mechanisms underpinning Wolbachia-mediated arboviral resistance in insects. Next, it will discuss how this strategy is currently being harnessed, and critically analyze the cost, safety, scalability, efficacy, and long-term impacts of these field releases. Thorough understanding of this technique will help expand and improve future deployments, as well as inform novel drug development using Wolbachia metabolites.