Dengue Fever, GMOsquitos, and a “Wolbachian” Invasion

In my recent Public Health Perspectives post for PLOS Blogs, I discussed two ways to control the transmission of dengue fever. The first was through the release of genetically-modified (GM) male mosquitoes that mate with wild females and pass on a gene that is lethal to its offspring–a strategy called Release of Insects carrying a Dominant Lethal (RIDL) (1). If released in sufficient numbers, the GM male mosquitoes will cause a collapse of the mosquito population.

Diagram of the RIDL transgene (image from Oxitec website)

Diagram of the RIDL transgene (image from Oxitec website)

The RIDL transgene (a) that has been engineered into the OX513A strain of mosquitoes carries instructions for the production of a protein called tetracycline transactivator (tTA). tTA , itself, is a product of genetic engineering, created by the fusion of parts of two proteins. One “half” of tTA acts as transcriptional activator–it can turn on and amplify the expression of certain genes. The other “half” can bind to specific DNA sequences called tetO binding sites. By engineering tetO binding sites into the RIDL transgene this allows the tTA protein, itself, to amplify expression of the tTA gene thereby producing even more tTA protein (b). This results in what is known as a positive feedback loop. At high enough levels, the tTA protein interferes with cellular process causing mosquito larvae to die. The expression of the tTA gene can be turned off by tetracycline, however (c). Tetracycline binds to the tTA protein and prevents it from binding to DNA, which short circuits the feedback loop.

“This allows scientists to raise the mosquitoes in the lab by adding tetracycline to the diet of the larvae. Without a source of tetracycline in the wild, however, any mosquito offspring that inherits the gene will live not beyond the larval stage.”

The other strategy I discussed was using Wolbachia infection of mosquitos to prevent dengue transmission. Wolbachia is an symbiotic bacteria that has been shown to protect mosquitos against dengue infection by interfering with the ability of the dengue virus to replicate. Wolbachia can invade and establish itself in insect populations quite rapidly and stably–an ideal characteristic if Wolbachia is to be used in limiting the transmission of dengue. It accomplishes this by employing a cunning strategy called “cytoplasmic incompatibility (2).” In short, when Wolbachia-infected males mate with uninfected females all their offspring die. However, the offspring of Wolbachia-infected females are viable regardless of the infection status of the male. This means that Wolbachia infection confers a reproductive advantage to infected females over uninfected females–infected females are more likely to have offspring because they can mate with both infected and uninfected males. Furthermore, Wolbachia infection is passed on from mother to offspring. It is through this process that Wolbachia “invades” and secures its place in an insect population.

Field studies conducted in Australia showed that when  mosquitoes infected with the wMel Wolbachia strain are released into the wild, within several months stable wMel infection became established in two wild A. aegypti populations (3). The speed at which wMel invaded the natural mosquito populations demonstrated the potential of using Wolbachia infection to control the spread of dengue.

You can read more about this topic here:

Could Wolbachia be an alternative to dengue-fighting GMOsquitos?

References:

1) Phuc HK, Andreasen MH, Burton RS, Vass C, Epton MJ, Pape G, Fu G, Condon KC, Scaife S, Donnelly CA, Coleman PG, White-Cooper H, Alphey L. Late-acting dominant lethal genetic systems and mosquito control. BMC Biol. 2007 Mar 20;5:11. PubMed PMID: 17374148; PubMed Central PMCID: PMC1865532.

2) Walker T, Johnson PH, Moreira LA, Iturbe-Ormaetxe I, Frentiu FD, McMeniman CJ, Leong YS, Dong Y, Axford J, Kriesner P, Lloyd AL, Ritchie SA, O’Neill SL, Hoffmann AA. The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature. 2011 Aug 24;476(7361):450-3. doi: 10.1038/nature10355. PubMed PMID: 21866159.

3) Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, Greenfield M, Durkan M, Leong YS, Dong Y, Cook H, Axford J, Callahan AG, Kenny N, Omodei C, McGraw EA, Ryan PA, Ritchie SA, Turelli M, O’Neill SL. Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission. Nature. 2011 Aug 24;476(7361):454-7. doi: 10.1038/nature10356. PubMed PMID: 21866160.

Featured image:
Detail from the original by Emil August Goeldi (1859 – 1917) [Public domain or Public domain], via Wikimedia Commons

by Viet Le

3 responses to “Dengue Fever, GMOsquitos, and a “Wolbachian” Invasion

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