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Stunning Feature of Life-shortened Aedes

January 2, 2010 - 22:24 -- Mark Benedict

I know this web site is MALARIA World. But the field of genetic control of vectors is so small that I hope you will indulge me in a blog that reaches into arbovirology and highlights the kind of technology we might anticipate against Plasmodia in Anopheles. Genetic control of vectors received another Christmas gift when a bonus remarkable phenotype due to Wolbachia infection - in addition to cytoplasmic incompatibility (CI) and life shortening - was reported in Cell.

An Australian/Brazilian team has demonstrated that Ae. aegypti infected with the Wolbachia, POP-Cla, which was of interest initially for its life-shortening effect on females and CI, has a third documented and unquestionably useful phenotype. Moreira et al. demonstrated that infection also greatly reduces or prevents dengue (DENV) and chikungunya (CHIKV) virus infection. The interference is strong, direct and is not dependent solely on life-shortening. (Of somewhat lesser interest but still significant for Malaria World readers, is that Plasmodium gallinaceum infections are also reduced in these mosquitoes.) The method by which such a mosquito could be used to reduce disease transmission in a public health context is by population replacement: the Wolbachia infection would be introgressed into wild populations of mosquitoes by release of females. Concurrent population suppression would minimize any potential for a contribution (however unlikely) to disease transmission, pestiferousness and to increase the rate of introgression. (As a note of comfort to those who may be shocked by this idea, from what I am familiar with, the groups are performing exemplary due diligence not only scientifically, but in terms of biosafety and community engagement. There is no premature rush to release.) All well and good thus far. How does this new observation affect application? According to the authors: “The observed interference effect reported here appears sufficiently strong that it would act in conjunction with the life-shortening effect to control arbovirus transmission. Life-shortening effects on mosquitoes would become secondary and only act on individuals that might escape the direct viral interference effect. The combined action of two distinct Wolbachia effects, lifespan reduction and virus interference, should also reduce the risk of resistance formation to the strategy.” Keep in mind: the life-shortening effect was the first-sought “feature,” but now, the team knows there is a third trait that is possibly (and likely) more powerful. Is life-shortening now a feature or a bug? Does life-shortening multiply or divide the punch of this application? In terms of direct effects of released mosquitoes, having both anti-viral features will provide less chance of infection than one alone. On that count it’s a feature for biosafety. With regard to the larger vision of establishing the Wolbachia in wild populations in area-wide control, unless it absolutely and exhaustively replaces the wild type mosquitoes, life-shortening will reduce the likelihood of success – the feature has become a bug. It is my hope that eventually invasions will NOT be controlled in order to provide an inoculation effect beyond the initial release location. If the direct viral inhibition and CI are sufficient to prevent disease and to spread, would one want life-shortening? No. Even though the fitness loss may be small, it will reduce the rate of spread and increase the likelihood that mosquitoes that do not carry the infection persist. Until more release experience is gained, such population spread inhibition will provide a kind of containment. In the long term, the research team should be testing other Wolbachia that have minimal effects on fecundity but similar direct effects on viruses and that maintain CI. Regardless, timing is everything, and this advance will provide added biosafety characteristics and public assurance for tests that are expected within the next couple of years. The hand of cards that can be played in genetic control just picked up an ace.