Mutation Fired Outbreak of Deadly Tropical Virus

What a difference a nucleotide makes. A simple change in the genetic sequence of the chikungunya virus may have triggered a massive outbreak of the deadly tropical disease on an island in the Indian Ocean in 2005 and 2006. The mutation made it easier for the virus to reproduce inside the mosquitoes that transmit it to humans, researchers report in the current issue of PLOS One.
Chikungunya kills about one in every 1000 infected people; in the rest, it can cause rash, fever, and crippling joint and muscle pains. The outbreak at La Réunion, a French island 700 kilometers east of Madagascar, sickened at least a third of the 800,000 inhabitants (ScienceNOW, 17 February 2006). "The scope and magnitude were really unprecedented," says Ann Powers, an expert in insect-borne viruses at the Centers for Disease Control and Prevention in Fort Collins, Colorado. The virus was spread mainly by the Asian tiger mosquito, Aedes albopictus, although it wasn't known at the time as a prominent chikungunya vector.
From sequencing the RNA genomes of viruses isolated from patients, researchers knew that chikungunya had undergone a mutation early on in the epidemic. The mutation led to a one-amino-acid change within E1, a protein sitting on the viral coat. About September 2005, most patients still had the amino acid alanine at a certain position within E1. But from about December on, when the outbreak really got going, more than 90% had valine at that same position. Researchers suspected that the change had facilitated spread, but this was mostly speculation.
Now they have proof. A group led by Anna-Bella Failloux of the Pasteur Institute in Paris bred populations of A. albopictus mosquitoes from La Réunion and nearby Mayotte and fed them a blood meal spiked with virus having one or the other version of E1. The scientists then ground up the insect bodies at different time intervals after the feeding and measured the amount of virus inside. In mosquitoes fed with the valine-substituted E1, the virus occurred in quantities almost 100 times higher than in those without. This mutated virus was also better able to pass the wall of a mosquito's midgut and make its way to the salivary glands, from where it could pass to a new victim with the insect's next bite. Apparently, the mutation made the virus a much better fit for La Réunion's Asian tiger mosquito population and thus made the epidemic soar, says Failloux.
"It's an elegant study," says Powers. "They did a very nice job of showing that there is a difference in what was occurring early in the outbreak and later on." That said, many other factors must have conspired to fuel the epidemic, Powers says, from zero immunity in the human population--La Réunion was virgin territory for chikungunya--to the fact that the mosquitoes were apparently thriving at the time.