Researchers have discovered the key to how a mysterious mosquito-borne viral outbreak swept over the Indian Ocean island of La Reunion in 2005 and 2006, infecting about 266,000 people and causing at least 260 deaths - the first fatalities to be reported in connection with the virus, known as chikungunya.
University of Texas Medical Branch at Galveston (UTMB) scientists proved that a single mutation in the virus glycoprotein E1 made it more infectious and facilitated its transmission by a mosquito species found on La Reunion and neighboring islands — one not previously involved in chikungunya outbreaks. The species, Aedes albopictus, is commonly known as the Asian tiger mosquito; it established itself in the United States about 20 years ago and has recently spread to southern Europe.
Chikungunya virus normally causes extreme arthritis-like joint pain, which can occasionally last for months or years. It takes its name from an African tribal word meaning “that which bends up,” a reference to the contorted, stooped posture some of its victims assume.
“Chikungunya virus had been known to be primarily carried by a different mosquito, Aedes aegypti, which is not found on La Reunion,” said UTMB professor Stephen Higgs, senior author of a paper on the discovery appearing online Dec. 7 in PloS Pathogens , a peer-reviewed open-access journal published by the Public Library of Science. “Adaptation to Aedes albopictus and introduction to a human population that had never been exposed to the virus before set everything up for this outbreak.”
Numerous tourists became infected, many of whom carried chikungunya home with them. Although the La Reunion strain of the virus did not cause a subsequent outbreak in Europe, Higgs said, it could have done so. In fact, another strain of the virus responsible for an ongoing outbreak in India has spread to Aedes albopictus mosquitoes and humans in Italy.
The UTMB researchers focused their attention on a single-amino acid change in the La Reunion chikungunya strain and found that this E1 A226V mutation led to increased virus infectivity for Aedes albopictus. To further prove the role of this mutation, lead author and graduate student Konstantin Tsetsarkin inserted that change into a chikungunya strain collected in West Africa in 1983, and then showed that it dramatically increased the virus' ability to infect Aedes albopictus.
“After we finished with the infectivity experiments, we analyzed the ability of the virus to disseminate to mosquito salivary glands and then be transmitted by mosquitoes,” Tsetsarkin said. “Then we simultaneously infected Aedes albopictus mosquitoes with equal amounts of the mutant virus and the original strain, and we saw that the virus with the E1 A226V mutation was predominately transmitted over the other one — the mutation gave the La Reunion strain an evolutionary advantage in Aedes albopictus, enabling it to out-compete the other strain.”
The key mutation, Tsetsarkin said, was linked to the virus' dependence on cholesterol in mosquito cell membranes, a key factor in the virus' ability to infect those cells and spread to mosquito salivary glands. Like other mosquito-borne viruses, chikungunya spreads to humans in mosquito saliva when the insects bite people.
“This is such a simple genetic change — the equivalent of a missing comma in a six-page short story — and yet it facilitated a huge epidemic,” Higgs said. “With Aedes albopictus already present in so many countries and likely to spread to others, perhaps helped by global warming, this shows us that we need to be ready for the possibility that chikungunya will soon be spreading to other locations as well.”