Dengue Fever, and associated dengue hemorrhagic fever, is emerging globally as the most important arboviral disease threatening human populations. Approximately 2.5 billion people are at risk of the disease and each year an estimated 50-100 million cases occur. Moreover, this disease continues to both expand into temperate climates and increase in severity. The virus is transmitted to humans by the mosquitoes Aedes aegypti and Aedes albopictus. In the U.S., Ae. albopictus is present in 36 states while Ae. aegypti is found in several southern states. Experience elsewhere in the world shows that the disease's occurrence usually follows where the mosquitoes are breeding. At the present time, no treatment or vaccine is available for dengue fever leaving vector control as the primary intervention tool. One such method is population replacement, in which natural mosquito populations would be replaced with modified populations that are unable to transmit the dengue virus. It is in this aspect that the endosymbiotic bacterium Wolbachia has shown great potential to be used as a vehicle for introducing disease-resistance genes into mosquitoes, or to directly reduce the mosquito's ability to transmit the pathogen.
Our long-term goal is to develop Wolbachia-based control strategies to block dengue virus transmission in mosquitoes. Toward this, we will identify factors that enable Wolbachia-based population replacement to succeed in a way that reduced vectorial capacity for dengue viruses. Specifically, we are interested in:
The mosquito immune responses to dengue viruses and Wolbachia
The potential interactions between dengue viruses and Wolbachia in mosquitoes
The molecular mechanism of Wolbachia-induced cytoplasmic incompatibility in mosquitoes
The improved Wolbachia-based mosquito population replacement and suppression
Our lab owns a state-of-the-art insectary and BSL-2 facility to work on dengue virus in both mosquito and cell culture. We have strong expertise in the functional genomic assay, including microarray, RNA inteference and mosquito transgenesis. Our lab is also one of the leaders on Wolbachia transfection via embryo microinjection.
Zhiyong Xi’s work with mosquitoes and Wolbachia bacteria was highlighted in MSU President's report. See the video linked here. Dr. Xi and his colleagues are developing strategies that bring us closer than ever to eradicating dengue virus transmission in mosquitoes.
Industry Expertise (5)
Areas of Expertise (6)
Combating Zika and Future Threats Grand (professional)
Awarded by USAID
University of Kentucky: Ph.D., Medical Entomology 2005
China Pharmaceutical University: B.S., Biopharmaceutics 1991
Bacteria-Treated Mosquitoes Released in More Locations
Last month, CNN reported that researchers had released these mosquitoes on a Chinese island. “So far, members of [Zhiyong] Xi's team claim that they have suppressed the mosquito population on the island by a whopping 96%, but scientists have questioned whether he will be able to scale up his island experiment in larger areas,” according to CNN. Xi said he wants to expand to more populated areas and to Mexico...
Inside China's 'Mosquito Factory' Fighting Zika and Dengue
Zhiyong Xi is a man on a mission.
He wants to rid China -- and potentially the world -- of mosquitoes, specifically the ones that carry devastating diseases like Zika and dengue. And he's doing it in the classic style of good versus evil.
"We're building good mosquitoes that can help us fight the bad ones," the entomologist said in his 3,500-square-foot laboratory in Guangzhou, China.
Decked out in white scrubs, Xi, a soft-spoken researcher from Michigan State University, gestures at hundreds of trays, each filled with about 6,000 squirming mosquito larvae. The room reeks of ground beef liver powder cut with yeast, a superfood for the tiny creatures...
This Lan Releases Two Million Mosquitos a Week for Science
Aedes albopictus is the world’s most invasive mosquito. It’s responsible for most of the mosquito-borne disease in China, and spreads Zika, Dengue and yellow fever around the world. For the past four years, scientists at this laboratory, run by Yat-Sen University and Michigan State University, have released hundreds of millions of Wolbachia-infected mosquitoes on nearby islands. Lab director Zhiyong Xi says recent surveys of the mosquito populations at testing and control sites have shown suppression rates as high as 99 percent...
Why Researchers are Releasing Millions of Mosquitoes to Combat the Zika Virus
The Washington Post
The man behind this government-backed experiment is Zhiyong Xi, professor at Sun Yat-sen University and Michigan State University. Inside the fluorescent compound in Guangzhou, China, Xi and a team of researchers are experimenting with using the biology of the Aedes mosquito against itself...
Zhiyong Xi: A Dream of Wiping Out Dengue Fever
Zhiyong Xi is an assistant professor in the Department of Microbiology and Molecular Genetics and director of the Sun Yat-sen University–Michigan State University Joint Center of Vector Control for Tropical Diseases. He is working to eradicate dengue fever, a disease that afflicts up to 100 million people each year. His work with mosquitoes and Wolbachia bacteria is putting him closer to his goal...
Journal Articles (5)
In the same way that infection with the bacteria Wolbachia spp. can make Aedes mosquitoes resistant to dengue virus, there have been hints that these bacteria can interfere with the reproduction of malaria parasites. Bian et al. (p. 748) established a heritable Wolbachia infection in anopheline mosquitoes, which simultaneously suppressed the reproduction of malaria parasites within the adult female mosquitoes. The results hold promise for developing the model into a biocontrol agent to assist malaria control...
Wolbachia is a maternally transmitted endosymbiotic bacterium that is estimated to infect up to 65% of insect species. The ability of Wolbachia to both induce pathogen interference and spread into mosquito vector populations makes it possible to develop Wolbachia as a biological control agent for vector-borne disease control. Although Wolbachia induces resistance to dengue virus (DENV), filarial worms, and Plasmodium in mosquitoes, species like Aedes polynesiensis and Aedes albopictus, which carry native Wolbachia infections, are able to transmit dengue and filariasis. In a previous study, the native wPolA in Ae. polynesiensis was replaced with wAlbB from Ae. albopictus, and resulted in the generation of the transinfected “MTB” strain with low susceptibility for filarial worms. In this study, we compare the dynamics of DENV serotype 2 (DENV-2) within the wild type “APM” strain and the MTB strain of Ae. polynesiensis by measuring viral infection in the mosquito whole body, midgut, head, and saliva at different time points post infection. The results show that wAlbB can induce a strong resistance to DENV-2 in the MTB mosquito. Evidence also supports that this resistance is related to a dramatic increase in Wolbachia density in the MTB's somatic tissues, including the midgut and salivary gland. Our results suggests that replacement of a native Wolbachia with a novel infection could serve as a strategy for developing a Wolbachia-based approach to target naturally infected insects for vector-borne disease control.
Wolbachia is a maternal transmitted endosymbiotic bacterium that is estimated to infect up to 65% of insect species. The ability of Wolbachia to both induce viral interference and spread into mosquito vector population makes it possible to develop Wolbachia as a biological control agent for dengue control. While Wolbachia induces resistance to dengue virus in the transinfected Aedes aegypti mosquitoes, a similar effect was not observed in Aedes albopictus, which naturally carries Wolbachia infection but still serves as a dengue vector. In order to understand the mechanism of this lack of Wolbachia-mediated viral interference, we used both Ae. albopictus cell line (Aa23) and mosquitoes to characterize the impact of Wolbachia on dengue infection. A serial of sub-lethal doses of antibiotic treatment was used to partially remove Wolbachia in Aa23 cells and generate cell cultures with Wolbachia at different densities. We show that there is a strong negative linear correlation between the genome copy of Wolbachia and dengue virus with a dengue infection completely removed when Wolbacha density reaches a certain level. We then compared Wolbachia density between transinfected Ae. aegypti and naturally infected Ae. albopictus. The results show that Wolbachia density in midgut, fatbody and salivary gland of Ae. albopictus is 80-, 18-, and 24-fold less than that of Ae. aegypti, respectively. We provide evidence that Wolbachia density in somatic tissues of Ae. albopictus is too low to induce resistance to dengue virus. Our results will aid in understanding the mechanism of Wolbachia-mediated pathogen interference and developing novel methods to block disease transmission by mosquitoes carrying native Wolbachia infections.
We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at ∼1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of ∼4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of ∼2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
Mosquitoes are vectors of parasitic and viral diseases of immense importance for public health. The acquisition of the genome sequence of the yellow fever and Dengue vector, Aedes aegypti (Aa), has enabled a comparative phylogenomic analysis of the insect immune repertoire: in Aa, the malaria vector Anopheles gambiae (Ag), and the fruit fly Drosophila melanogaster (Dm). Analysis of immune signaling pathways and response modules reveals both conservative and rapidly evolving features associated with different functional gene categories and particular aspects of immune reactions. These dynamics reflect in part continuous readjustment between accommodation and rejection of pathogens and suggest how innate immunity may have evolved.