Genome of mosquito that spreads West Nile virus, encephalitis and elephantiasis decoded

Breeding in drains, cesspools and other polluted water bodies, Culex quinquefasciatus feeds on blood from birds, livestock and humans and transmits West Nile virus, St. Louis encephalitis and the microscopic roundworm that causes lymphatic filariasis, leading to 120 million infections and over 40 million cases of elephantiasis each year.

Mapping the genome of the Southern house mosquito effectively completes a platform for mosquito comparative genomics -- a critical third piece of a genetic puzzle researchers have sought to solve in a global effort to contain the spread of infectious diseases transmitted by mosquitoes, according to co-authors of the first of two new reports.

Already, researchers have sequenced the genomes of two other mosquitoes, Aedes aegypti, which transmits yellow fever and dengue fever, and Anopheles gambiae, a species that carries malaria, a disease that infects 250 to 500 million people each year and kills nearly one million people annually, mostly young children in sub-Saharan Africa.

Culex differs from the two other arthropods in that its molecular "parts list" includes a staggering 18,883 protein-coding genes -- that is 22 percent larger than for Ae. aegypti and 52 percent larger than for An. gambiae -- with multiple gene family expansions, including those controlling smell and taste, immune responses and genes that attack toxic foreign compounds, the researchers discovered.

Greater understanding of these expanded gene sets could provide critical new insights into Culex and improve public health efforts. The mosquito's more complex genetic structure may have influenced evolution of Culex as an opportunistic feeder, able to detect and feed on birds, humans and livestock. This flexibility contributes to Culex's ability to transmit numerous disease-causing organisms -- including West Nile virus, encephalitis viruses, filiarial worms and malaria parasites -- to birds and humans, the researchers report.

"The consequent diversity in many different genes may be an important factor that led to the wide geographic distribution" of Culex, concludes a team of 69 co-authors of the genome report.

Armed with the genome sequence, researchers undertook the next step of uncovering the building blocks coded in the Culex genome that make it a deadly transmitter of disease, said Boston College DeLuca Professor of Biology Marc A.T. Muskavitch, a co-author of the first report and the senior author of the second, which was produced by an international team of 33 researchers.

"With the genome decoded, we have the building blocks. We can also determine which building blocks the mosquito uses to combat a pathogen and which genes the pathogen avoids when evading the defenses of the mosquito," said Muskavitch, who began collaborating with colleagues at the Broad Institute in 2007.

Researchers were able to analyze for the first time a set of 25 mosquito-pathogen interactions involving mosquito-borne viruses, filarial worms, malaria parasites and bacteria in all three mosquitoes. The analysis revealed common and distinct responses to these pathogens by the three and gave further credence to the theory that "mosquito-born pathogens have evolved to evade the innate immune responses in three vector mosquito species of major medical importance."

In the cases of Culex and Aedes aegypti, both are armed with hundreds of genes capable of triggering an immune response to the West Nile and encephalitis viruses. Instead only a few disease-fighting proteins respond in either mosquito, said Muskavitch, thereby allowing the viruses to take hold.

"Viruses fly under the radar of the mosquito's RNA interference infection response system -- which should be defending it," he said. "Viruses have actually developed ways to evade the vast majority of the infection response systems of both Culex and Aedes aegypti."

Similar results were found when researchers examined the immune responses to filarial worms and bacteria.

Muskavitch said the genome advances are being shared with scientists around the globe as part of an international effort to bring researchers, doctors and public health experts the best information possible in order to combat the spread of these deadly and disfiguring diseases.

"Our goal is to determine how we can turn the building blocks of these mosquitoes against pathogens, in attempts to defeat those pathogens," Muskavitch said. "That is the scientific and public health significance of this new research."