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Aedes Agypti Mosquito's Immune System Revealed

The immune system of this mosquito is of great importance as scientists believe it plays a key role in controlling the transmission of viruses that cause yellow and dengue fevers – diseases that infect over 50 million people worldwide every year.The genes that make up the immune system of the Aedes aegypti mosquito which transmits deadly viral diseases to humans have been identified.

This study is the first of its kind on the newly-sequenced genome of the Aedes aegypti mosquito, which is also published in this week's Science. The researchers identified over 350 genes which are involved in the Aedes mosquito's immune system, and discovered that they evolve much faster than the rest of the genes in the genome.

Identifying which of these key genes are implicated in the transmission of viral diseases is an area of future research that could lead to new ways of combating these diseases. One possibility would be to affect the activity of the genes and therefore help the mosquitoes fight off the viruses more effectively, preventing transmission to humans.

Imperial College scientists participating in this study established previously that other mosquitoes do have a robust immune system that can either allow or block transmission of malaria parasites. Further research will be needed to ascertain whether some of the newly discovered genes in Aedes may provide a similar defence mechanism that can fight the disease viruses.

Dr George Christophides of Imperial's Division of Cell and Molecular Biology, senior author on the paper explains: "Our study has revealed the genetic 'landscape' made by parts of this mosquito's newly-sequenced genome which are involved with immunity.

By working to understand as much as possible about these genes, and the way they interact with specific pathogens, we hope to gain a more complete understanding of the mechanisms by which a pathogen either survives inside the insect body, or is killed by the insect's defences."

The international research team, led by Imperial PhD student Robert Waterhouse, focused on comparing the immunity genes of the Aedes mosquito with similar groups of genes in the harmless fruit fly and the Anopheles mosquito that transmits malaria.

When comparing the two different mosquitoes, the scientists found some similarities in the genes controlling their respective immune systems, but also numerous differences. The team aims to discover which of these genetic differences could explain why one type of mosquito transmits dengue and yellow fevers, while the other transmits malaria. Beyond the present descriptive work, functional studies will be needed to clarify exactly how this happens.

"This study made us realise that the immune systems of insects are not static but evolve and differentiate rapidly, most likely in response to the different pathogens which each insect species encounters", says Dr Christophides.

Professor Fotis Kafatos, senior researcher of Imperial's immunogenomics lab and co-author of the paper, explains the significance of their study, saying: "Understanding the genetics behind pathogen/immune system interactions in disease vector mosquitoes may help us understand why, for example, some types of mosquitoes can transmit a particular human pathogen while others cannot.

If those that cannot have evolved an effective immune system that fights off the pathogen, we may be able to use this knowledge to enhance specific reactions of the immune systems in other mosquitoes to control the spread of the disease".

Source-EurekalertJAY/M

Mosquito-Borne Diseases

There are four distinct stages in the life cycle of a mosquito – egg, larva, pupa, and adult. The mosquito has a different appearance at each stage. The entire cycle generally takes one to two weeks, but the time can vary depending on the species and environmental conditions such as temperature.

The adult female can produce eggs at intervals throughout her life, but she requires proteins from a blood meal in order for the eggs to develop. Depending on the species of mosquito, the female lays between 30 and 300 eggs at a time; the Aedes mosquito, for example, generally lays 100 eggs at a time.

Many mosquitoes deposit their eggs directly on the surface of water, either singly (Anopheles) or clumped into rafts (Culex); others lay their eggs above the waterline, often in manmade containers (Aedes).

The water level must rise, as a result of rainfall or other means, to cover the eggs before the larva can hatch. The larvae feed on microorganisms in the water and go through a series of stages in which they molt and enlarge. At the end of this period, the larva changes into a comma-shaped pupa. The pupa does not feed and spends most of its time at the surface of the water.

When the pupa has matured, the pupal skin splits and a fully developed adult mosquito emerges. Adult mosquitoes feed mostly on flower nectar, but the females need to acquire a blood meal to continue the replication cycle.

If the female bites a person who is infected with Zika virus or another virus, the mosquito will pick up the virus. The virus reproduces within the mosquito for a certain period of time in which the virus migrates from the mosquito's gut through the circulatory system to the salivary gland. Then, the mosquito can pass the virus to another person during a subsequent bite.

It is thought that warmer climates and denser population centers provide mosquitoes with greater availability to habitats in which they prefer to live and breed, especially for those species such as the Aedes mosquitoes that have adapted to human environments. Not only has the geographic range of mosquitoes expanded, but within urban areas there are more numerous sites containing standing water - such as buckets, flower pots, and old tires - that mosquitoes require to complete their life cycle.

These favorable settings accelerate the progression of mosquitoes through their life cycle, as well as shortening the incubation period within the mosquitoes that viruses need to reproduce.

This May Be The Deadliest Creature On Earth

We squash mosquitoes with our enormous hands. We poison-bomb them from spray trucks and airplanes. We irradiate them, drain their habitats, breed them experimentally in laboratories to confound their DNA. We've known for more than a century that a mosquito's bite can pass on brutal disease: Zika is the virus receiving the most attention now, but malaria alone kills more than 400,000 people a year, and scores of thousands die from mosquito-borne yellow fever and dengue. To this day, insects smaller than a child's thumbnail remain the most dangerous nonhuman animals on the planet.

And we are still trying to figure out how to vanquish them. There's a line one hears frequently from entomologists and other mosquito experts, especially amid the Zika alarms: "We have no silver bullet." What they really mean is no stake through the heart; silver bullets are for werewolves. Mosquitoes—some of them, anyway—are vampires. Of the 3,500 species that researchers have identified so far, only a few hundred feed on human blood, including the Zika-carrying Aedes aegypti and Aedes albopictus. Some, notably Ae. Aegypti, turn out to be assailants of astonishing formidability.

Start with their physical equipment, especially in the mosquitoes that are the most anthropophagous, which is an elegant way of saying they prefer human blood. A mosquito homes in on you by sensing the proximity of blood from your sweat, your breath, your warmth. Her feeding apparatus, that elaborate proboscis, is a multipart marvel with a skin-piercing fascicle of tiny stylets that can suck your blood while injecting mosquito saliva laced with an anticoagulant. A mosquito can slip that fascicle into your skin so gently that you have no idea what's happening until the blood meal is already under way. She can sip your blood until she's more than twice her weight and has to lumber off someplace to rest, jettisoning the liquid and retaining the nutrients, before she can fly properly again.

Yes, your vampire is always a female. In the mosquito world, males live off plants. The female is the biter, the worker, the source of human peril; she lives off plants too, but all those blood nutrients are for her eggs, the nourishing and laying of which are the great project of her short, purposeful, and somewhat solitary life. A single mating may be all an Ae. Aegypti needs; she stores sperm inside her body, fertilizing separate batches of eggs as needed, up to several hundred at a time. Five or six occasions of egg laying are common for an Ae. Aegypti that escapes extermination by swat or insecticide and reaches her expected month-long life span. The multiplication possibilities are staggering.

Ask biologists what natural advantage different mosquito species might have gained by spreading disease—why Aedes became the primary carrier of the Zika virus, for example, and Anopheles the carrier of malaria parasites—and they're likely to tell you that you're thinking about the question backward. It's the pathogens, those disease-causing organisms driven to multiply in mammalian bodies, that over millennia "learned," evolutionarily speaking, what excellent transport and delivery services some mosquitoes happen to provide. It's not an easy ride for the pathogens: They have to survive being sucked into a mosquito's gut, exposed to digestive enzymes, and then pushed through membranes into a mosquito salivary gland before being injected into the next warm-blooded host. The injectors, on the other hand, are simply perpetuating their family line. "It's such a rare confluence of evolution that has allowed this to happen," says Karl Malamud-Roam, a mosquito research scientist who helps direct a pest management program based at Rutgers University. "It's hard to be a successful germ or mosquito."

A modicum of respect seems in order, then, for this remarkable confluence and the very resourcefulness of the flying vampires. Consider the reproductive strategies of Aedes aegypti, which because of Zika has been the subject of international symposia and plans of attack. An Ae. Aegypti will lay her eggs in the random bodies of water that humans tend to create just by living day to day: A pet dish will do, or an upturned jar top, a discarded tire, a cistern with a cracked lid. She will spread each egg batch around, making it much harder for natural or man-made interventions to wipe out a whole brood at once. She can find egg-laying spots that aren't wet yet but will be, when the weather changes; she's that ingenious. She bites all day long; bed nets (which have helped reduce worldwide malaria deaths because the malaria-carrying Anopheles tends to bite at night) aren't as effective against Zika and other Aedes-carried diseases.

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