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.