Kwabena Boahen Asare ’25, Health Sciences, 22X
Figure: Female Aedes Aegypti mosquito sucking human blood.
Image Credit: Wikipedia Commons
Flaviviruses like Zika and Dengue naturally survive through virus-vector interactions. The vectors of flaviviruses are arthropods, such as mosquitoes, that suck the blood of their vertebrate hosts to nourish their eggs and in turn, release these viruses into the bloodstream of their hosts. When naïve arthropods suck the blood of these infected hosts, they are infected with the viruses, and the cycle continues (Kupferschmidt, 2016).
Busula et al. (2017) established that malaria-induced odors on hosts can augment their attraction to mosquitoes. Similarly, Takken and Knols (1999) found that volatiles i.e., chemicals compounds that vaporize readily, were one of the fundamental host cues for manipulating hematophagous (blood-sucking) vectors. Other evidence also suggests that the spectrum of host odorants is shaped through infection and inflammatory responses. For instance, Plasmodium, the malaria-causing parasitic protozoan, produces an isoprenoid precursor which increases the release of volatile blends by human red blood cells thus affecting the feeding and blood-sucking behaviors of mosquitoes (Emami et al., 2017).
Using mice models, 60 female Aedes aegypti mosquitoes, and a 3-cage olfactometer assay, 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 Tropical and Subtropical Animal Virus Disease Laboratory, and the Chinese Center for Disease Control and Prevention found that approximately 70% of mosquitoes had an affinity for the Zika-infected mice, relative to 30% for uninfected mice, suggesting that mosquitoes preferred the Zika-virus-infected mice over the uninfected ones. The experiment was repeated with Dengue-infected mice with similar results. The researchers then repeated this experiment, but with a 2-port olfactometer assay. This was to reduce the mosquitoes’ entry point, to determine if the results would be consistent. The outcome revealed a positive mosquito-response result for the Zika-infected mice, correlating with that of the previous experiment with the 3-cage olfactometer assay (Hong et al., 2022).
In a 1980 study by Gillies, carbon dioxide was described as a potent mosquito-host-seeking activator. However, post-Zika infection, carbon dioxide (CO2 ) levels decreased in mice due to their deteriorating physiological status but did not change in mice infected with Dengue. As the results of the various cases of the olfactometer experiments were similar, it was evident that another activator was more potent in attracting mosquitoes (Gillies, 1980).
Through analyzing the volatile emissions of the infected mice, Zhang et al. found that decanal, styrene, and acetophenone elicited significant electrophysiological responses. They then applied these compounds to different mice skins and repeated the olfactometer experiments; acetophenone attracted the most mosquitoes. Acetophenone was then applied to human hands and similar results were seen. They also found that dengue-infected patients produced more acetophenone.
Acetophenone production occurs through the suppression of the expression of an essential antimicrobial protein, RELMa, by Bacillus bacteria on host skin (Verhulst et al., 2011). A potential strategy for arboviral (arthropod-borne viral) disease control was also tested by the authors. Dietary administration of isotretinoin, a Vitamin-A derivative, in the flavivirus-infected animals reduced acetophenone production and made the animals less attractive to the mosquitoes (Zhang et al., 2022).
Taken together, the results of this study indicate that host odorants, particularly acetophenone, are partially responsible for hematophagous arthropods’ host-seeking motivation. There remains, however, a need for further research to determine whether the above holds true for real-life situations, how flaviviruses suppress RELMa, and whether there are other effective anti-arboviral remedies.
References
Zhang, H., Zhu, Y., Liu, Z., Peng, Y., Peng, W., Tong, L., … Cheng, G. (2022). A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness. Cell. https://doi.org/10.1016/j.cell.2022.05.016
Busula, A. O., Bousema, T., Mweresa, C. K., Masiga, D., Logan, J. G., Sauerwein, R. W., et al. (2017). Gametocytemia and Attractiveness of Plasmodium falciparum–Infected Kenyan Children to Anopheles gambiae Mosquitoes. The Journal of Infectious Diseases, 216(3), 291–295. https://doi.org/10.1093/infdis/jix214
Robinson, A., Busula, A. O., Voets, M. A., Beshir, K. B., Caulfield, J. C., Powers, S. J., et al. (2018). Plasmodium-associated changes in human odor attract mosquitoes. Proceedings of the National Academy of Sciences, 115(18), E4209–E4218. https://doi.org/10.1073/pnas.1721610115
Emami, S. N., Lindberg, B. G., Hua, S., Hill, S. R., Mozuraitis, R., Lehmann, et al. (2017). A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. Science, 355(6329), 1076–1080. https://doi.org/10.1126/science.aah4563
Takken, W., & Knols, B. G. J. (1999). ODOR-MEDIATED BEHAVIOR OF AFROTROPICAL MALARIA MOSQUITOES. Annual Review of Entomology, 44(1), 131–157. https://doi.org/10.1146/annurev.ento.44.1.131
Gillies, M. T. (1980). The role of carbon dioxide in host-finding by mosquitoes (Diptera: Culicidae): a review. Bulletin of Entomological Research, 70(4), 525–532. https://doi.org/10.1017/s0007485300007811
Verhulst, N. O., Qiu, Y. T., Beijleveld, H., Maliepaard, C., Knights, D., Schulz, S., Smallegange, R. C. (2011). Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes. PLoS ONE, 6(12), e28991. https://doi.org/10.1371/journal.pone.0028991
University of Connecticut. (2022, June 30). Some viruses make you smell tastier to mosquitoes: Dengue and Zika viruses alter the microbiome in both mice and humans to attract mosquitoes and spread to new hosts. ScienceDaily. Retrieved August 15, 2022 from www.sciencedaily.com/releases/2022/06/220630114511.htm