Zika and dengue viruses alter the scent of the mice and humans they infect, the researchers report in the June 30 issue of Cell. The altered odor attracts mosquitoes, which bite the host, drink its infected blood, and then carry the virus to its next victim.
Dengue is spread by mosquitoes in tropical areas around the world and occasionally in subtropical areas such as the southeastern US. It causes fever, rash, and aching pain, and sometimes bleeding and death. More than 50 million cases of dengue fever and about 20,000 deaths occur each year, most of them in children, according to the National Institute of Allergy and Infectious Diseases at the National Institutes of Health (NIH).
Zika is another mosquito-borne viral disease in the same family as dengue. Although it is rare for Zika to cause serious illness in adults, a recent outbreak in South America caused serious birth defects in the fetuses of infected pregnant women. Yellow fever, Japanese encephalitis, and West Nile virus are also members of this family of viruses.
These viruses require continuous infections in animal hosts and mosquitoes to spread. If either of these are missing, if all susceptible hosts shed the virus, or if all mosquitoes are killed, the virus is gone. For example, during the yellow fever outbreak in Philadelphia in 1793, the arrival of fall frosts killed the local mosquitoes and the outbreak ended.
In tropical climates without killing frost, there are always mosquitoes; the virus only needs one to bite an infected animal host to spread. The Zika and dengue viruses seem to have developed a sneaky way to up the odds.
A team of researchers from UConn Health, Tsinghua University in Beijing, the Institute of Infectious Diseases in Shenzhen, the Ruili Hospital of Chinese Medicine and Dai Medicine, the Yunnan Laboratory of Tropical and Subtropical Animal Virus Diseases, and the Chinese Center for Disease Control and Prevention, suspected that dengue and Zika might be manipulating hosts in some way to attract mosquitoes. Both malaria and general inflammation can change the smell of people. Dengue and Zika viral infection, they thought, could do the same.
First, the team tested whether the mosquitoes showed a preference for infected mice. And indeed, when the mosquitoes were offered a choice between healthy mice or dengue-sick mice, the mosquitoes were more attracted to the dengue-infected mice.
They then analyzed the smelly molecules in the skin of infected and healthy mice. They identified several molecules that were more common in infected animals and tested them individually. They applied them both to clean mice and to the hands of human volunteers and found that an odor molecule, acetophenone, was especially attractive to mosquitoes. Skin odors collected from human dengue patients showed the same thing: more attractive to mosquitoes and more acetophenone production.
Acetophenone is produced by some Bacillus bacteria that grow on human (and mouse) skin. Normally, human skin produces an antimicrobial peptide that keeps bacilli populations in check. But it turns out that when mice are infected with dengue and Zika, they don’t produce as much antimicrobial peptide and the bacillus grows faster.
“The virus can manipulate the skin microbiome of hosts to attract more mosquitoes and spread faster!” says Penghua Wang, an immunologist at UConn Health and one of the study’s authors. The findings could explain how mosquito viruses manage to persist for so long.
Wang and his co-authors also tested for preventive potential. They gave mice with dengue fever a type of vitamin A derivative, isotretinoin, known to increase the production of the skin’s antimicrobial peptide. Isotretinoin-treated mice emitted less acetophenone, which reduced their attractiveness to mosquitoes and potentially lowered their risk of infecting others with the virus.
Wang says the next step is to test more human dengue and Zika patients to see if the connection between skin odor and the microbiome is generally true under real-world conditions, and to see if isotretinoin reduces acetophenone production in sick humans, as well as in the sick. mice.
Source: today.uconn.edu