The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature

School of Biological Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
Nature (Impact Factor: 41.46). 08/2011; 476(7361):450-3. DOI: 10.1038/nature10355
Source: PubMed


Dengue fever is the most important mosquito-borne viral disease of humans with more than 50 million cases estimated annually in more than 100 countries. Disturbingly, the geographic range of dengue is currently expanding and the severity of outbreaks is increasing. Control options for dengue are very limited and currently focus on reducing population abundance of the major mosquito vector, Aedes aegypti. These strategies are failing to reduce dengue incidence in tropical communities and there is an urgent need for effective alternatives. It has been proposed that endosymbiotic bacterial Wolbachia infections of insects might be used in novel strategies for dengue control. For example, the wMelPop-CLA Wolbachia strain reduces the lifespan of adult A. aegypti mosquitoes in stably transinfected lines. This life-shortening phenotype was predicted to reduce the potential for dengue transmission. The recent discovery that several Wolbachia infections, including wMelPop-CLA, can also directly influence the susceptibility of insects to infection with a range of insect and human pathogens has markedly changed the potential for Wolbachia infections to control human diseases. Here we describe the successful transinfection of A. aegypti with the avirulent wMel strain of Wolbachia, which induces the reproductive phenotype cytoplasmic incompatibility with minimal apparent fitness costs and high maternal transmission, providing optimal phenotypic effects for invasion. Under semi-field conditions, the wMel strain increased from an initial starting frequency of 0.65 to near fixation within a few generations, invading A. aegypti populations at an accelerated rate relative to trials with the wMelPop-CLA strain. We also show that wMel and wMelPop-CLA strains block transmission of dengue serotype 2 (DENV-2) in A. aegypti, forming the basis of a practical approach to dengue suppression.

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    • "Wolbachia infections can induce a number of different phenotypes in their hosts, including interfering with host reproduction to promote their own transmission (Hurst et al. 1999, Rousset et al. 1992, Stouthamer et al. 1999, O'Neill and Karr 1990, Riegler et al. 2005, Hoffmann et al. 2011). Recent studies have found that several Wolbachia strains can block either the replication or the pathogenicity of RNA viruses, including dengue viruses (DENVs), in insect hosts (Hedges et al. 2008, Teixeira et al. 2008, Moreira et al. 2009, Osborne et al. 2009, Glaser and Meola 2010, Bian et al. 2010, Frentiu et al. 2010, Walker et al. 2011, Mousson et al. 2012). However, not all Wolbachia strains show antiviral effects. "
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    ABSTRACT: The endosymbiotic bacterium Wolbachia pipientis infects many species of insects and has been transinfected into the mosquito Aedes aegypti (L.), the primary vector of dengue virus (DENV). Recently, it has been shown that Wolbachia blocks the replication and transmission of RNA viruses, such as DENV, in a number of mosquito species including Ae. aegypti and Aedes albopictus (Skuse), which is naturally infected with Wolbachia and considered a secondary vector for DENV. The mosquito species Aedes notoscriptus (Skuse) is highly prevalent in Australia, including in areas where DENV outbreaks have been recorded. The mosquito has been implicated in the transmission of Ross River and Barmah Forest viruses, but not DENV. We investigated whether Wolbachia naturally infects this mosquito species and whether it has an impact on the ability of Ae. notoscriptus to transmit DENV. We show, for the first time, that Ae. notoscriptus is naturally infected with a strain of Wolbachia that belongs to supergroup B and is localized only in the ovaries. However, Wolbachia infection in Ae. notoscriptus did not induce resistance to DENV and had no effect on overall DENV infection rate or titer. The presence of a native Wolbachia in Ae. notoscriptus cannot explain why this mosquito is an ineffective vector of DENV.
    Full-text · Article · Dec 2015 · Journal of Medical Entomology
    • "Increasing attention has been paid to controlling the spread of dengue by targeting mosquito longevity by introducing genetically modified mosquitoes or introducing endosymbiotic Wolbachia bacteria to shorten the mosquito lifespan [3] [5] [6]. That is, Wolbachia-infected mosquitoes are released to create a sustained infection in the wild (uninfected) population. "
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    ABSTRACT: Wolbachia is a genus of endosymbiotic bacteria that can infect mosquitoes and reduce their ability to transmit dengue virus. Although the bacterium is transmitted vertically from infected mothers to their offspring, it can be difficult to establish an endemic infection in a wild mosquito population. We developed and analyzed an ordinary differential equation model to investigate the transmission dynamics of releasing Wolbachia-infected mosquitoes to establish an endemic infection in a population of wild uninfected mosquitoes. Our transmission model for the adult and aquatic-stage mosquitoes takes into account Wolbachia-induced fitness change and cytoplasmic incompatibility. We showed that, for a wide range of realistic parameter values, the basic reproduction number is less than one. Hence, the epidemic will die out if only a few Wolbachia-infected mosquitoes are introduced into the wild population. Even though the basic reproduction number is less than one, an endemic Wolbachia infection can be established if a sufficient number of infected mosquitoes are released. This threshold effect is created by a backward bifurcation with three coexisting equilibria: a stable zero-infection equilibrium, an intermediate-infection unstable endemic equilibrium, and a high-infection stable endemic equilibrium. We analyzed the impact of reducing the wild mosquito population before introducing the infected mosquitoes and observed that the most effective approach to establish the infection in the wild is based on reducing mosquitoes in both the adult and aquatic stages.
    No preview · Article · Sep 2015
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    • "Resistance to pyrethroid insecticides, the primary insecticide family used against adult mosquitoes, is particularly worrying in the context of the re-emergence of dengue and other arboviruses worldwide (Bhatt et al. 2013). Although attempts are made to develop new insecticides or alternative mosquito control strategies (Scholte et al. 2004; Lacey 2007; Hoffmann et al. 2011; Walker et al. 2011; Harris et al. 2012), their large-scale implementation in tropical regions will require at least a decade. Until this, characterizing molecular mechanisms underlying resistance is crucial for tracking down resistance alleles and improving resistance management strategies (Corbel et al. 2013). "
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    ABSTRACT: The capacity of mosquitoes to resist insecticides threatens the control of diseases such as dengue and malaria. Until alternative control tools are implemented, characterizing resistance mechanisms is crucial for managing resistance in natural populations. Insecticide biodegradation by detoxification enzymes is a common resistance mechanism; however, the genomic changes underlying this mechanism have rarely been identified, precluding individual resistance genotyping. In particular, the role of copy number variations (CNVs) and polymorphisms of detoxification enzymes have never been investigated at the genome level, although they can represent robust markers of metabolic resistance. In this context, we combined target enrichment with high-throughput sequencing for conducting the first comprehensive screening of gene amplifications and polymorphisms associated with insecticide resistance in mosquitoes. More than 760 candidate genes were captured and deep sequenced in several populations of the dengue mosquito Ae. aegypti displaying distinct genetic backgrounds and contrasted resistance levels to the insecticide deltamethrin. CNV analysis identified 41 gene amplifications associated with resistance, most affecting cytochrome P450s overtranscribed in resistant populations. Polymorphism analysis detected more than 30,000 variants and strong selection footprints in specific genomic regions. Combining Bayesian and allele frequency filtering approaches identified 55 nonsynonymous variants strongly associated with resistance. Both CNVs and polymorphisms were conserved within regions but differed across continents, confirming that genomic changes underlying metabolic resistance to insecticides are not universal. By identifying novel DNA markers of insecticide resistance, this study opens the way for tracking down metabolic changes developed by mosquitoes to resist insecticides within and among populations.
    Full-text · Article · Jul 2015 · Genome Research
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