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  • Dengue fever is a mosquito-borne disease caused by a virus of the same name.

  • It's a part of the Flaviviridae family, known for its other famous members: Yellow

  • Fever, West Nile, and Zika.

  • It's also referred to as breakbone fever, but that should be the least of your concern...what

  • you need to worry about is a complete.

  • system.

  • shutdown.

  • Most commonly found in tropical regions, Dengue puts 40-50% of the global population at risk.

  • With symptoms ranging from fever, rashes, painful joint and muscle aches to vomiting,

  • Dengue can resemble the flu, but it can become life-threatening in a much different way.

  • When the pH changes, it changes the configuration of the Dengue virus.

  • Actually, at that point I could grab the model.

  • Great.

  • Okay, thank you.

  • Cool, all right.

  • Dengue prop.

  • I'm Shannon Bennett.

  • I work at the California Academy of Sciences.

  • I'm curator of microbiology and chief of science, and I study the genetic makeup of Dengue viruses.

  • I've been working on it since 2000 and I was one of the first people to look at large swaths

  • of the Dengue virus genome to pinpoint where key mutations were occurring to drive its

  • spread and pathogenicity.

  • To understand how Dengue spreads, it helps to start with how it gets in.

  • Enter, the mosquito: specifically a species called Aedes aegypti.

  • It's a day-biting mosquito.

  • It actually prefers the crepuscular times of the day, so that's dawn or dusk, and it

  • will feed on multiple people.

  • It might feed three or four times in its lifetime, and that gives the Dengue virus ample opportunity

  • to be passed between human hosts by a single infected female mosquito.

  • Now, what makes these types of viruses so quick to take off, is their genetic architecture,

  • which allows them to begin producing proteins immediately after they enter the host cell.

  • Dengue virus has been an interesting puzzle for a lot of scientists and clinicians.

  • It is probably infecting almost 400 million people a year as far as we know, but only

  • a small fraction of people actually get sick, about 90 million a year.

  • So we're not really sure why some people get sick and other people don't get sick.

  • Once the Dengue virus gets in through the skin, it can take several days to a week eventually

  • find its way into your lymph nodes and, then, bloodstream.

  • From there, it's just one big fast-track to Flavivirus-town.

  • So Dengue's primary target and the way it sustains itself in your body is in white blood

  • cells, and these are macrophages and monocytes that are antibody receptor-bearing cells that

  • the Dengue virus uses to bind and enter the cell.

  • The cell is naturally taking anything that's bound to its receptors and phagocytizing it,

  • so basically pulling it into an internal cellular capsule, and once that happens, the pH of

  • that capsule changes.

  • And when the pH changes and that lock-and-key relationship between the virus protein and

  • the host cell receptor proteins experience that change in pH, a pore is formed... and

  • through that pore, the virus genome enters into the host's cytoplasm.

  • And from there it's a pretty sophisticated version of copy and paste.

  • The virus uses the host cell to duplicate itself.

  • Or as Dr. Bennett describes it, budding.

  • In contrast, many people are familiar with other mosquito-borne diseases like malaria.

  • Malaria is a burster.

  • At the sporozoite stage as it's replicating in your red blood cells, it's copying itself

  • to a great degree until basically your host cell explodes or bursts open and spreads sporozoites

  • around.

  • Dengue virus doesn't do that.

  • It's a budder.

  • It's working with the host cell and taking advantage of host cell energy and metabolism

  • to create new virus particles.

  • Dr. Bennett and her team study the genetic differences between the four serotypes of

  • Dengue.

  • Those differences and similarities are what makes co-circulating stereotypes a dangerous

  • combination, contributing to more severe episodes of the illness.

  • They are co-circulating today all over the world, but in the old days they didn't overlap

  • so much.

  • When they started to move around...we also saw more hemorrhagic fever and more severe

  • forms of the disease, so one hypothesis is because we're being exposed to multiple strains

  • of Dengue throughout our lifetime and that's creating this risk to develop severe disease.

  • And yes, hemorrhagic fever is just as bad as it sounds.

  • So what happens in a secondary infection is that those antibodies that you've produced

  • to the first one don't bind as efficiently to the Dengue virus.

  • Instead of being neutralized in the endosome, it can enter the host cell more efficiently

  • and create more virus.

  • What we think is happening is that it's creating more infected cells than you would have in

  • the case of a primary infection or a re-exposure to that same primary serotype because of the

  • inefficiency and the lack of perfect match between the antibody and the new virus.

  • Typically, once your immune system fights off a disease, it remembers it for future

  • encounters.

  • Usually that works.

  • But with Dengue, immunity to one serotype doesn't protect you against a different

  • serotype, and can in fact enhance the infection, making a second or even third encounter with

  • the disease much worse...because your immune system's memory is stimulated but not a

  • great match.

  • We think that that is what's causing this out of control immune response that accelerates

  • and eventually leads to the hemorrhagic fever that we see and even in some cases shock syndrome.

  • So Dengue shock syndrome is another severe outcome of this over-reactive proinflammatory

  • immune response.

  • One impact of having an overabundance of proinflammatory cytokines is that membranes become leaky,

  • and when capillary beds become leaky, blood will flow out.

  • And you start to bleed out into your capillary beds and into the tissues, and then fluids

  • to flow into your bloodstream causing potentially hypovolemic shock and death by Dengue shock

  • syndrome.

  • And both hypovolemic shock and fever can be deceptive.

  • The most frustrating phenomenon with Dengue virus is that people seem to start to recover.

  • They might have three to four to maybe seven days of fever depending on when they first

  • exhibit symptoms, and then the fever's starting to go down, we can sort of see the diminishment

  • of symptoms, and then hemorrhagic fever or shock syndrome can kick in very quickly after

  • that.

  • So Dengue is not something to take lightly, but Dr. Bennett says these extreme cases are

  • still pretty rare.

  • Of the nearly half a billion cases reported annually, only 500,000 are severe, with many

  • countries reporting less than 1% fatality rate.

  • Still, knowing the symptoms and ways to help prevent initial infection are key.

  • And while there is a vaccine, there's still a long way to go.

  • The challenge with developing a vaccine for Dengue is that you need to develop a vaccine

  • that's effective against all four serotypes simultaneously, and this is very unusual.

  • There are vaccines that can vaccinate against all four types, but they don't do it to the

  • equivalent level.

  • So you might be mostly immune to one and then a little immune to some of the other stereotypes,

  • and that too is not what we want.

  • So stay tuned.

Dengue fever is a mosquito-borne disease caused by a virus of the same name.

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