Female mosquitoes are predators of mammalian blood, relying on blood proteins to lay their eggs. While certain mosquito species are attracted to mammals by their emission of body heat and carbon dioxide, other species, such as Anopheles gambiae and Aedes aegypti, have evolved a strong lust for the smell of humans. Such mosquitoes are also deadly vectors that contribute to the efficient spread of human diseases such as malaria, Dengue hemorrhagic fever, West Nile fever, and chikungunya, with the latter two commonly known as urban epidemics.  

Given the role of mosquitoes as vectors of human epidemic, scientists sought to determine how mosquitoes (such Aedes aegypti) are attracted to humans, what can be done to ward off these bugs, and what causes mosquitoes to pick up viruses contributing to human epidemic. The month of May 2013 marks the publication of three key breakthroughs in PLOS and Nature, providing answers to these pressing questions, and arming humans with the ability to keep mosquito bites and human epidemics at bay. 

Genetics Explain Mosquito’s Lust for the Smell of Humans
May 2013 marks the publication of the first paper on mosquito genetics, and the first genetic feat beyond the classical lab insect Drosophila. The study, published in the online issue of Nature, is also a much more meaningful use of insect genetics, allowing scientists to use functional genetics to understand how nature’s disease-carriers are drawn to the smell of humans. In this study, Dr. Leslie Vosshall (Rockefeller University) discovered an olfactory receptor that is crucial for the mosquito’s ability to detect humans, and to tell humans apart from other mammals. Vosshall further discovered that although the mutation of this receptor does not affect the mosquitoes’ ability to detect their mammalian prey (through detection of carbon dioxide and body heat), the mutation curbed the mosquitoes’ long-evolved lust for the smell of humans. The mosquitoes  carrying the mutant olfactory receptors, named “orco”, and are no longer attracted to the smell of floral or honey odors, or repelled by the smell of the insect repellent DEET ((N,N-diethyl-meta-toluamide). However, the “orco” bugs still retain the ability to taste DEET, being repelled only upon direct contact with a DEET-bearing surface. The study shows the first functional evidence suggesting that the olfactory receptor is crucial for the mosquitos’ ability to detect humans, and thus may be an ideal strategic target to reduce A. aegypti’s attraction to humans.

Malaria-Bearing Mosquitoes are Even More Attracted to Human Odors
Interestingly, while the mosquito species  An. gambiae and A. aegypti are innately attracted to humans, it appears that malaria-bearing mosquitoes are even more attracted to smelly human odor (like smelly socks); an interesting discovery published in the May 15, 2013 issue of PLOS One. In this study, Dr. James Logan and colleagues at John Hopkins University discovered that An. gambiae demonstrates a much stronger lust for human odor when it is infected with the malaria parasite Plasmodium falciparum. The effect was so significant that the malaria-infected mosquitoes demonstrated a 3-fold higher attraction to smelly human odor compared to uninfected mosquitoes; an attraction measured by how many times the mosquitoes landed on the “smelly socks” used in the experiment. Logan further suggested that the malaria infection likely causes protein alterations in the olfactory receptors, rendering the receptors more receptive to human odors. The suggestion was well-founded on a previous discovery where malaria infection was shown to alter 12 protein spots in the mosquito’s olfactory system. Indeed, the new-found mosquito-genetics in Vosshall’s lab may be the ideal platform to further investigate how malaria influences the mosquito’s lust for the smell of humans, and whether mutational strategies can help prevent this. 

The study also provides scientists with a rare glimpse of how the malaria parasite is influencing the mosquitoes’ attraction to humans, and ultimately exploiting the vector to enhance its transmission to humans.  “At the moment, we only have these glimpses of how parasites are manipulating the mosquitoes,” said Dr. George Christophides, chair of infectious disease and immunity at Imperial College London. “We need to exploit that information to help us control malaria.”  One such exploitation may be to use smelly socks as an effective odor trap to attract malaria-bearing mosquitoes, diverting these vectors from their intended human target, and ultimately prevent these vectors from transmitting malaria to humans.

Cool Temperatures Produce Disease-Bearing Mosquitoes
Lastly, another breakthrough published in the May 30, 2013 issue of PLOS Neglected Tropical Disease showed that mosquitoes reared in cool temperatures would increase their likelihood to pick up viruses contributing to human disease. Dr. Kevin Myles and Virginia Tech University discovered that Aedes aegypti has a considerably weaker immune system when reared in cooler temperatures, increasing its susceptibility to viral infections, and ultimately its likelihood to become vectors of human-diseases. The immune system of the mosquito is comprised of interference RNA, which is essentially an antiviral machine that works by suppressing the expression of viral genes. The study is the first example showing that cold temperatures can reversibly impair the anti-viral interference RNA system in mosquitoes, and ultimately the mosquito’s defense against viral infection. The discovery can help explain the rapid transmission and outbreaks of West Nile and chikungunya viruses in unexpected urban areas in cooler regions of the globe, such as New York (1999), Italy (2007), and France (2010).  "Our data offers a plausible hypothesis for how changes in weather influence the transmission of these diseases and will likely continue to do so in the future," says Myles.

Mosquito-Genetics to Study Mosquitoes and Vector-borne diseases
The above studies are stunning revelations on the role of olfactory receptors in mosquitoes’ attraction to humans, the role of malaria parasites in enhancing/exploiting mosquitoes’ lust for human smell to promote the its transmission in humans, and the influence of temperature on mosquito’s susceptibility of becoming disease-bearing vectors. The new-found mosquito-genetics platform in the Vosshall lab at the Rockefeller University could enable scientists to further elucidate the precise molecular mechanisms behind the deadly interaction between diseases, mosquitoes, and men. Such understanding can help humans control vector-borne diseases by predicting the emergence of disease-bearing mosquitoes, and diverting these mosquitoes from their intended human targets.

DeGennaro, M. et al. (2013) orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. Nature. 2013 May 29. doi: 10.1038/nature12206 

Smallegange R.C., et al. (2013) Malaria Infected Mosquitoes Express Enhanced Attraction to Human Odor. PLoS ONE 8(5): e63602. doi:10.1371/journal.pone.0063602

Adelman Z.N. et al. (2013) Cooler Temperatures Destabilize RNA Interference and Increase Susceptibility of Disease Vector Mosquitoes to Viral Infection. PLoS Negl Trop Dis 7(5): e2239. doi:10.1371/journal.pntd.0002239

Image credit:  DeGennaro, M. et al. (2013) orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. Nature. 2013 May 29. doi: 10.1038/nature12206