Amber Fang

Independent Research Pd. 2

Olfactory Senses: Key to ZIKV

Before 2014, no one had heard of Zika virus. But within a year hundreds of thousands of

cases of Zika swept through Brazil, making it the largest target for a scientific cure. One of the

main research areas for a cure is to target the olfactory senses of mosquitoes that carry the virus.

The olfactory senses, also known as the sense of smell is currently a hot area of research for

scientists because of its incredible potential to help stop disease transmission of various mosquito

species. The olfactory senses of the Aedes aegypti(A. aegypti) mosquito and the human

emanations that attract them will play a key role in decreasing the Zika virus (ZIKV) epidemic

because it can help scientists to create a more effective form of bait, a more effective way to

prevent mosquito bites, and is interdependent with a deeper insight into the understanding of

mosquito anatomy.

Zika virus is an arbovirus, a virus that can be spread by mosquitoes and includes dengue

and yellow fever. ZIKV is transmitted by the A. aegypti mosquito. It was first discovered in 1947

in Uganda, and was thought to cause benign human infections in Africa and Asia. It has since

been documented in Yap Island in 2007 and the French Polynesia in 2013 before circulating to

the Americas (Enfissi et al.). ZIKV usually has no symptoms, and when they are expressed, it is

very mild and only lasts 5 -7 days. The real danger of ZIKV applies to pregnant women. In a

case report done by Mlakar et al., they examined cases of pregnant women infected with ZIKV

and the development of their fetuses, and discovered that there is a very strong connection

between ZIKV and microcephaly, a disease in which abnormal brain development occurs in
fetuses, causing them to have significantly smaller heads than expected. The evolving nature of

the virus and its dangers makes it all the more important that a cure is discovered. There are

many different solutions that have been proposed and much research surrounding ZIKV, the

most prominent of them being the olfactory senses of mosquitoes.

Using the olfactory senses of the A. aegypti and human attractants can help create a more

effective form of bait. The A. aegypti use human emanations to orient themselves towards

humans, which allows them to spread viruses such as Zika virus. Doing a chemical study of these

emanations can provide new ideas for the formation for attractant blends (Bernier et al.,

Synergistic Attraction of Aedes Aegypti"). There are many possible attracts and chemical

compounds that stimulate the aedes olfactory senses, but Geier, Bosch, and Boeckh performed

an experiment showing that ammonia is a promising candidate for an attractant, especially in

combination with lactic acid. Air-borne chemical cues are also used by mosquitoes in locating a

host. Takken performed an experiment on these cues, and discovered that CO2 is heavily

involved in a majority of air-borne chemical cues used by A. aegypti ("Ammonia as an

Attractive Component of Host Odour").

By using the olfactory senses of mosquitoes, scientists can create an effective attractant

blend that can be used as a form of bait for the A. aegypti. However, it is also important to

understand the attractants of body odor to develop this bait (Takken). Geier, Sass, and Boeckh

were trying to identify the components odor that play a role in identification of host location, and

in doing so discovered that CO2 combined with L-lactic acid acts as a synergistic attractant

(Olfaction in Mosquito-Host Interactions). The goal of these scientists is to mimic the human

scent to develop a powerful lure that can be used as bait in mosquito traps, which requires
knowledge of the olfaction on both the mosquito and human sides. Conor McMeniman of Johns

Hopkins University and his team are planning to use two-photon microscopy to see which of the

chemicals of human scent activate the olfactory centers of the mosquito brain (Staff, Hub).

Although there is a lot of progress being made in the field in terms of olfaction, Takken

writes that still, little is known about the chemical compounds and specific attractants that

contain these olfactory cues. There are many different candidate attractants, of which some are

found to be weak attractants of A. aegypti (Bernier et al., Chemical Analysis Of Human Skin

Emanations). While many candidates of attractants have been discovered, Geier, Sass, and

Boeckh write that results for experiments pertaining to olfactory senses may not be conclusive

(Olfaction in Mosquito-Host Interactions). Learning more about olfaction in mosquitoes is a

crucial first step towards creating solutions that can prevent transmissions of diseases such as

Zika virus.

There are many different solutions to ZIKV surrounding olfaction that are being

proposed. One solution besides creating a form of bait is by using the olfactory senses of the A.

aegypti and human attractants to create a more effective way to prevent mosquito bites. As there

are many variations in human attractions of mosquitoes, Geier, Bosch, and Boeckh write that

studying these variations can help to create a more effective repellent. However, Bernier et al.

discuss the complications they discovered when comparing emanations. They discovered that the

variation in human attraction of mosquitoes indicates that mosquito behavior varies over time

and that a relative difference exists in the ability of people over time to attract mosquitoes

(Chemical Analysis Of Human Skin Emanations), which is why it is crucial to learn more about

the variation in mosquito senses and human emanations.

 There is one company that believes they hold the key to an effective repellant. Jolly

writes about the Kite Patch, a patch that supposedly provides full body protection from

mosquitoes by confusing mosquito senses and not allowing the A. aegypti to locate humans

based on certain olfactory cues. Although the author was unable to discover what the exact blend

in the patch was, she did find out that it worked by confusing mosquitoes senses. There are many

more tests that need to be performed before the Kite Patch can be widely distributed, but it shows

that mosquito olfaction and orientation are very important. This is why Geier, Sass, and Boeckh

conducted experiments in an attempt to identify the components odor that play a role in

identification of host location, concluding that an understanding of the attractants of human body

odor is important to preventing location of a host for A. aegypti. Takken extends on this idea by

writing about the distinction between short and long range attraction of air-borne chemical cues

that blood seeking mosquitoes use to locate a host, in which CO2 is involved in both processes.

Unlocking the key to the way mosquitoes orient themselves towards a host is critical,

because olfactory cues are widely used by bloodsucking insects to detect and find their sources

for blood meals(Geier, Bosch, and Boeckh, Ammonia as an Attractive Component of Host

Odour"). It is important to learn and understand the olfactory senses of A. aegypti, not only

because of the solutions it could discover, but because it is interdependent with a deeper insight

into the understanding of mosquito anatomy. Geier, Sass, and Boeckh discuss how these two

things are connected, writing that, Using mosquito olfactory cues, scientists can work to

discover the ways in which mosquitoes orient themselves to humans(Olfaction in

Mosquito-Host Interactions). Jolly addresses this when writing about the Kite Patch, saying that

looking at the blend in the Kite Patch will be helpful for determining the best combination of
attractants to confuse the olfactory responses of the A. aegypti. Takken furthers this, writing that

mosquitoes orient themselves using air-borne olfactory cues to locate a host, and discussing the

three groups that bodily emanations from the host that contain olfactory cues can be divided into:

skin emanations, exhaled air, and urine. He also writes that olfactory cues used by bloodsucking

insects to detect sources for meals can be used to increase understanding of mosquito anatomy.

This is because A. aegypti respond very quickly to host stimuli, so olfactory cues can be used to

increase understanding of how they do it(Geier, Sass, and Boeckh, Olfaction in Mosquito-Host

Interactions). Bernier et al. expand on this, writing that humans produce cues that are vital for

bloodsucking insects to locate a meal, and learning how they do so starts by increasing

knowledge of mosquito anatomy(Synergistic Attraction of Aedes Aegypti").

As a topic of heavy study due to the expansion of the Zika virus epidemic, Carey and

Carlson discuss the remarkable progress that has been made over the past decade in elucidating

mechanisms of insect olfaction, in many cases facilitated by the genetic tractability of model

organisms. Bohbot et al. discuss how systems such as insecticides and odor-baited traps can be

improved by improving understanding of relationship between the A. aegypti olfactory system

and odorants, focusing heavily on the insects physiological state and studying neural

coexpression from the C cell, a neuron that is suspected to be involved in olfaction in the

brain. Matthews et al. further this by writing about how exploring and analyzing the adult gene

expression in A. aegypti has important implications for vector control and sensory driven

behaviors. While it is understood that the effects of blood-feeding on gene expression are broad,

they attempted to identify gene expression changes correlated with blood-feeding to gain insight

into mechanisms of how a blood-meal may influence behavior. Thus, to design a solution to
ZIKV regarding olfaction, one must first understand the role anatomy plays in the spread of the

virus.

Olfactory senses of the A. aegypti and olfactory cues from humans could hold the key to

unraveling Zika virus. Not much is known about the way mosquitoes orient themselves towards

humans, or about the chemical compounds that attract them. Most research and experiments

regarding olfactory cues are inconclusive, but using existing research can help future

experiments to better grasp this evasive concept. Understanding is also vital to helping create

either a form of bait for mosquitoes to reduce mosquito-transmitted diseases or help prevent

mosquito bites in the first place. This can possibly be found in a new piece of technology called

the kite patch, which claims to prevent mosquito bites in its entirety simply by wearing it.

Although more research will be needed, it is a good starting place to do more research.
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