Gene sequence of Culex quinquefasciatus will be used in quest to understand disease transmission
An international research team has determined the DNA sequence of the mosquito species whose bite transmits West Nile virus, St. Louis encephalitis virus and the microscopic worm responsible for elephantiasis.
University of Texas Medical Branch at Galveston researchers played a vital part in the push to sequence the genome of Culex quinquefasciatus, applying expertise gained through more than a decade of studying the mosquito species and the viruses it spreads. The UTMB scientists collaborated with researchers at 38 other institutions on the project, including the University of California, Riverside, the European Bioinformatics Institute, Boston College and the Harvard School of Public Health.
“Culex pipiens quinquefasciatus is the most widely distributed mosquito in the world, and in terms of disease transmission to humans it’s one of the three most important mosquito species,” said UTMB professor Stephen Higgs, one of the authors of two papers related to the project that will appear in the Oct. 1 issue of Science. “This work gives us a terrific platform to improve our understanding of the dynamics of infection, which has to be done if we’re going to find ways to interrupt disease transmission.”
The other two mosquito species identified by Higgs as part of the “triad of the most important disease vectors” are Anopheles gambiae (which transmits malaria) and Aedes aegypti (yellow fever virus and dengue virus). The genome of Anopheles gambiae was published in 2002, and that of Aedes aegypti in 2007.
“This is really exciting for us, because we can finally perform experiments that we’ve wanted to do for seven or eight years,” said UTMB assistant professor Dana Vanlandingham, also an author of the Science papers. “Our basic question is why do certain mosquito species transmit a particular virus and other mosquito species do not? Why don’t they all carry all the viruses? We don’t know, but now we have three different systems for comparative studies to investigate interactions between viruses and mosquitoes.”
In the first of the Science papers (“Sequencing of Culex quinquefasciatus Establishes a Platform for Mosquito Comparative Genomics”), researchers announce that they have identified all of Culex quinquefasciatus’ 18,883 genes. Each gene can produce one of the proteins that make up the mosquito and determine its behavior — including the way its immune system responds to infection by viruses, bacteria and parasites.
The second paper (“Pathogenomics of Culex quinquefasciatus and Meta-Analysis of Infection Responses to Diverse Pathogens”) focuses specifically on that immune response. UTMB’s biosafety level 3 laboratories contributed significantly to its data on West Nile virus by allowing researchers to safely infect Culex mosquitoes with West Nile virus and then extract genetic material that provided information on the mosquitoes’ response to the virus.
“Culex quinquefasciatus is the main vector for West Nile — it’s common here along the Gulf Coast of Texas, but closely related species are found all over the country, and it bites both birds and humans,” Higgs said. “There have been about a million human infections with West Nile in the United States and, presumably, hundreds of millions of bird infections. Almost every one of those infections was started by a mosquito bite.” This year 24 human cases have been reported in Texas, with two deaths.
Higgs, Vanlandingham and their UTMB colleagues have been working on the relationship between Culex quinquefasciatus and West Nile ever since the virus first arrived in North America in 1999. “For years we’ve been looking at the interaction of viruses and mosquito gene expression in other mosquito species infected with various viruses, because those were the only systems that were available,” Vanlandingham said. “We’ve been able to see some parts of the Culex West Nile virus picture, but we haven’t had the appropriate tools for detailed genetic studies. This work will provide the base for a lot of people to investigate mosquito-borne pathogens, from multiple angles.”
The National Institutes of Health and the National Institute of Allergy and Infectious Diseases provided funding for this research.