Mosquito spit can increase dengue severity

A mosquito’s spit can be worse than its bite alone. In some cases, the insect’s saliva makes the viral disease dengue fever more severe, a new study finds.

In mice, scientists found that mosquito spit weakened blood vessels, making them more permeable, or “leaky.” Easier exchange between the blood and tissues may help the virus spread faster — and increase the severity of disease — immunologist Michael Schmid and colleagues report online June 16 in PLOS Pathogens.

Dengue virus enters the bloodstreams of nearly 400 million people a year, through the sharp proboscises of tropical Aedes mosquitoes, which also deliver a spit-load of other molecules as they slurp a meal. There are four strains of dengue, which can cause bone and muscle aches, high fever and, in severe cases, death. Overcoming one type of dengue doesn’t protect the host from the other three strains. In fact, subsequent infections are often worse (SN: 6/15/16, p. 22).

Immune cells fight off the first dengue infection, and the body develops antibodies to that strain. But during a subsequent episode with a different variety of dengue, the antibodies from the first infection don’t kill the second — they amplify it. They pull new virus into healthy cells.

Scientists have studied this strange immune trap for three decades, “but what we didn’t know was that saliva could exacerbate it,” says Schmid, now at the University of Leuven in Belgium.

Investigating spit is important, says virologist Eva Harris of the University of California, Berkeley, a coauthor of the study. Molecules in mosquito saliva “can modify and modulate the infection process,” she says. Saliva’s role is well-studied in other viral diseases, like West Nile, but not for dengue.

Schmid’s team inoculated mice either with virus, saliva, or both virus and saliva, during primary and secondary dengue infections. In primary infections, the severity of the disease did not differ substantially between treatments. Symptoms were mild, at most. But in secondary infections, the combination of virus and saliva was lethal to more than half of the mouse population. Without the saliva, mortality was much lower. 

To understand why, the researchers ran experiments to track viral spread through the circulatory system. In mouse ears, a molecule about the size of the dengue virus moved farther, and faster, when packaged with mosquito spit. And in the lab, human endothelial cells lining the inner walls of blood vessels sealed less tightly in the presence of Aedes saliva. The researchers also found that mice inoculated with virus alone could be rescued if the skin around the injection site was removed four hours later. The same procedure did not rescue mice dosed with virus and saliva.

These results should be interpreted with caution, says Duane Gubler, an infectious disease researcher at Duke University who was not involved in the study. Various environmental and genetic factors also play a role in the severity of the disease. “It’s not clear-cut,” he says.