Mosquitoes, Scents, and Viruses

Many viral diseases are spread via mosquitoes. Some of the more familiar viral diseases in the Americas that are transmitted by these insects include West Nile, Saint Louis encephalitis (SLE), Zika, and dengue fever. Mosquitoes are typically not the primary host for these viruses and are just vectors that carry the virus from animal to animal. For Saint Louis encephalitis virus and West Nile virus, the primary hosts are birds, while Zika has a broad host range and can infect many types of mammals, including humans. These viruses persist in the wild animal populations thanks to mosquitoes continually spreading the virus to new animals (Fig. 1).

Fig. 1. The sylvatic transmission cycle of mosquito-borne viruses. For some Saint Louis encephalitis virus and West Nile virus birds are the natural host. In nature, the virus is maintained by continual transmission from animal to animal via infected mosquitoes (sylvatic cycle). Humans are an incidental host in the sylvatic cycle who occasionally become infected when bitten by an infected mosquito. Incidentally infected humans rarely, if ever, pass on the virus to other humans. Created with BioRender.com.

Human cases of SLE and West Nile are incidental infections and are typically dead-ends that don’t spread to other humans. In contrast, humans are important reservoirs for Zika and dengue, and mosquitoes transmit these viruses from person to person (Fig. 2). 

Fig. 2. In the urban cycle, humans are the primary host for Zika and dengue viruses. The viruses are transmitted directly from human to human via mosquitoes without an animal host involved. Created with BioRender.com.

Mosquitoes acquire a virus when feeding on an infected animal or human. As a healthy mosquito takes a blood meal on its warm-blooded target, viruses in the target’s bloodstream are ingested along with the blood. The ingested viruses replicate in the mosquito’s gut, often amplifying the viral numbers to high levels. When the infected mosquito bites a new victim, viruses are passed to this new recipient, initiating another round of infection in the animal or human host. For all four of these viruses, the majority of human infections are asymptomatic although some individuals will develop serious, even life-threatening illnesses.

For diseases like Zika and dengue, viral persistence in the human population requires that mosquitoes bite infected individuals and carry the viruses on to other people. If an infected person is never bitten then the viruses in that person are lost as the person recovers or dies. A new study published in the journal Cell found that both Zika and dengue viruses cause changes in the scent of their human hosts to enhance the chance that an infected person will be bitten. Working first with mice, they found that infected animals gave off larger quantities of 11 odorant compounds compared to healthy animals. One of the compounds, acetophenone, is a mosquito attractant, and infected mice exuded 10 times more of this substance than the control mice. Similarly, dengue-infected humans also emit more of this molecule than healthy people and putting acetophenone on the skin of healthy volunteers made them more attractive to mosquitoes. These results suggest that increased amounts of this odorant may help ensure that mosquitoes preferentially bite infected individuals to facilitate viral spread, a very clever and insidious strategy evolved by these viral pathogens.

An important question is how a viral infection can change odorant production in an animal or human. Acetophenone in the skin is primarily produced by bacteria, and the quantity of these bacteria in the skin is controlled by a host protein called RELMa. Working again with mice, the investigators found that both Zika and dengue infections caused mice to produce less RELMa, which would allow the bacteria to proliferate to higher levels and produce more acetophenone. Interestingly, when infected mice were fed isotretinoin it increased RELMa production and reduced their attractiveness to mosquitoes. Isotretinoin is a vitamin A derivative used to treat acne and some cancers. Currently, there are no therapeutic drugs for patients with either Zika or dengue infections so infected individuals constitute a public health threat as they are a source for spreading new infections. It would be a great boon for dengue and Zika control if taking vitamin A or isotretinoin could lower the chance of infected people passing on the virus and thus reduce community spread.

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