Zika Virus Tricks Mosquitoes by Making Infected Humans Smell More Appealing

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMFeb 5 2025

Zika virus doesn’t just infect its hosts. It makes them more appealing to the very mosquitoes that spread it. A recent study published in Communications Biology revealed that the Zika virus (ZIKV) may alter human body odors, making infected individuals more attractive to mosquitoes.

In this study, a team of researchers from Europe discovered that human skin cells from infected individuals release distinct volatile organic compounds (VOCs), which enhance mosquito attraction and feeding behavior.

​​​​​​​Study: Zika virus modulates human fibroblasts to enhance transmission success in a controlled lab-setting. Image Credit: Corona Borealis Studio/Shutterstock.com

Background

Mosquito-borne diseases pose a major threat to global health, with viruses such as Zika, dengue, and malaria infecting millions every year. The transmission of these viruses depends on mosquitoes successfully locating and feeding on human hosts.

While factors such as body heat, carbon dioxide, and skin microbiota are known to influence mosquito attraction, recent research suggests that pathogens themselves may alter host cues to enhance their transmission.

Studies on malaria have shown that Plasmodium parasites manipulate mosquito feeding behavior, increasing their chances of spreading. Similarly, some viruses modify human skin microbiota to produce more attractive odors for mosquitoes.

However, the precise mechanisms behind these changes remain largely unknown. Understanding how ZIKV alters host odors could be instrumental in developing new interventions.

About the Study

In this study, the researchers conducted controlled laboratory experiments using human dermal fibroblasts infected with the ZIKV PE243 strain to investigate whether ZIKV infection in human skin cells alters VOC emissions, influencing mosquito behavior.

The infection was analyzed at two different time points: 10 hours post-infection, which represents the invasion stage, and 24 hours post-infection, which was during the transmission stage.

To identify changes in VOC production, the researchers collected air samples from infected and uninfected cell cultures using solid-phase microextraction. These samples were analyzed via gas chromatography-mass spectrometry to determine differences in chemical composition.

Additionally, to assess mosquito responses, female Aedes aegypti mosquitoes were exposed to synthetic VOC blends mimicking those emitted by infected cells.

Their attraction and feeding behaviors were tested in a dual-choice bioassay, where mosquitoes could choose between control and ZIKV-associated odor sources. Furthermore, the researchers used a wind tunnel experiment to track mosquito flight responses toward VOC-infused air streams.

The study also incorporated transcriptomic and proteomic analyses to explore the molecular mechanisms underlying odor changes.

Ribonucleic acid (RNA) sequencing was performed to examine gene expression shifts in infected cells, focusing on metabolic pathways linked to lipid synthesis and VOC production. Proteomic profiling was also conducted to identify enzyme alterations associated with volatile emissions.

Finally, statistical analyses, including Generalized Linear Mixed Models and survival analyses, were applied to determine significant differences in mosquito behavior, gene expression, and metabolic changes across experimental conditions.

The researchers used these multi-faceted approaches to provide a comprehensive understanding of how ZIKV infection alters host-derived chemical cues to enhance vector attraction and disease transmission.

Key Findings

The study found that ZIKV infection significantly altered the VOC profile of human fibroblast cells, leading to the increased release of mosquito-attractant compounds.

Chemical analysis identified elevated levels of hydrocarbons and oxidized compounds, including aldehydes and ketones, in infected cell cultures compared to uninfected controls.

Notably, compounds such as decanal, dodecanal, and sulcatone were significantly upregulated during the infection, particularly at the 24-hour transmission stage. Furthermore, the behavioral experiments confirmed that mosquitoes were more attracted to VOCs from infected cells.

In the dual-choice bioassays, the Aedes aegypti females displayed a strong preference for air streams containing ZIKV-related odors, with significantly higher landing and feeding rates compared to controls.

The wind tunnel experiments further revealed that mosquitoes exhibited increased flight activity and navigational precision toward infected-cell odor sources.

Further molecular analyses also showed that ZIKV infection triggered gene expression changes linked to lipid metabolism and VOC biosynthesis.

The transcriptomic data indicated upregulation of genes associated with lipid transport and fatty acid oxidation, suggesting that the virus manipulates host metabolic pathways to enhance volatile emissions.

Additionally, the proteomic analysis supported these findings, identifying increased expression of enzymes involved in lipid fragmentation, potentially contributing to the altered odor profile.

The infected mosquitoes were also observed to consume larger blood meals, likely increasing viral transmission potential.

This aligned with findings from previous studies on malaria parasites, which similarly influence vector-feeding behavior to optimize pathogen spread.

Conclusions

Overall, the results suggested that ZIKV enhances its transmission by inducing metabolic changes in human skin cells that produce odors that are more attractive to mosquitoes.

These findings offered a new perspective on virus-vector-host interactions and highlighted potential avenues for mosquito control, such as disrupting VOC-mediated attraction with targeted repellents or baited traps.