Wolbachia and arbovirus inhibition

1249 Arbovirus inhibition phenotype Arboviruses transmitted by mosquitoes have great importance in global health, owing to increasing ranges and impact and often with no effective vaccines or reliable prophylactics available. The most important is the flavivirus dengue virus (DENV), which occurs in 100 countries and causes tens of millions of cases of dengue fever annually, approximately half a million of which proceed to life-threatening hemorrhagic fever or shock syndrome [1]. Chikungunya virus (CHIKV), an alphavirus, is an important emerging pathogen in many regions of the world, and a number of epidemics with tens of thousands of cases or more have occurred in the last decade [2]. A dramatic transmission-blocking phenotype (e.g., no infectious viral particles could be detected in the mosquito saliva) for both viruses was observed in the mosquito Aedes aegypti, the most important vector of DENV. This vector was artificially transinfected with the wMelPop and wMel strains of the bacterial endosymbiont Wolbachia from Drosophila melanogaster [3–5]; inhibition of yellow fever virus was also observed in wMel-infected Ae. aegypti [5]. A wMel transinfection in Aedes albopictus blocked the laboratory transmission capacity for DENV [6] and CHIKV [7]. This species is often considered a secondary vector of DENV, although it has been the primary or sole vector in a number of epidemics, and is frequently a primary vector of CHIKV following an envelope protein mutation that significantly and specifically increased viral fitness in Ae. albopictus [8,9]. Interestingly, Wolbachia can also inhibit the transmission of some mosquito-borne parasites, such as Plasmodium by Ae. aegypti [3]. Wolbachia are intracellular and tend to be most concentrated in reproductive organs, but often have a wide tissue distribution within the host insect, including midgut and salivary glands. Arboviruses acquired in the blood meal must invade midgut cells and ultimately disseminate to the salivary glands to be transmitted, so Wolbachia and the virus can potentially be present within the same cells. Wolbachia itself is not an infectious agent, but is maternally transmitted in the egg cytoplasm and is able to invade host populations by manipulating their reproduction. The most widely observed reproductive phenotype (and the only one observed in mosquitoes) involves crossing sterilities known as cytoplasmic incompatibility. In the simplest case, consider crosses between Wolbachia-infected and uninfected individuals, early embryonic arrest occurs when uninfected females mate with infected males [10]; however, the offspring of infected females develop normally regardless of the male infection status, thus giving infected females a reproductive advantage. The self-spreading ability of Wolbachia makes it an attractive biocontrol agent to interrupt or reduce arbovirus transmission. A first field trial targeting wild populations of Ae. aegypti in northern Australia has proven successful in introducing the wMel strain to high population frequency [11]. A better understanding of the mechanisms of inhibition of DENV and CHIKV by Wolbachia Wolbachia and arbovirus inhibition in mosquitoes