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Chickenpox and shingles totally should not be the same thing.
One is an itchy rash you get in childhood if you weren’t vaccinated.
And one is a totally-different-seeming bout of blisters and nerve pain
that usually happens decades late/ in life.
Yet both are caused not just by the same virus,
but by the same incidence of the same virus.
That’s because chickenpox is caused by one of a group of viruses who excel
at making themselves into unwelcome guests… for life.
But this particular virus has an even weirder way of doing things.
Let’s take a look at how it pulls off this annoying double feature.
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If you’ve had chickenpox, then you’ve experienced one of the many types of herpesvirus.
For most people, chickenpox is an unpleasant but bearable childhood experience.
Though there is a rare risk of complications requiring hospitalization.
Since the introduction of the chickenpox vaccine in 1995, cases of chickenpox
in the United States, as well as hospitalizations, have dropped by over 95%.
But infections still remain incredibly high, at over 90% worldwide, since most
countries don’t include the chickenpox vaccine in routine childhood immunization.
Though this figure technically includes some people
who were vaccinated with a weakened version of the virus.
If you’re one of the people unlucky enough to have had chickenpox,
you might remember an uncomfortable 4 to 7 days as your body
fought off the virus, and the relief when the symptoms finally cleared up.
But, unlike most other viral infections, just because the symptoms are gone,
that doesn’t mean the virus is.
Herpesviruses like to move in and stick around, sometimes for life.
So it's not that unusual for a herpesvirus to infect you,
get comfy, and reoccur years later.
No, we're not gonna talk about that herpes,
but another friend you might have made in college: mono.
Epstein-Barr virus is another kind of herpesvirus responsible for
the fatigue-inducing, feverish, aching nightmare of mononucleosis,
or mono as it’s often known.
During the initial infection, EBV hitches a ride in various immune cells,
where it borrows one of our own genes to boost its replication.
Eventually your immune system is able to
take out the intruder, and the symptoms clear up.
But EBV doesn’t die off as you’d expect, oh no.
It’s just lying in wait.
After a miserable 2-4 weeks of mono as your body fights the infection,
the virus goes dormant in those immune cells it infected.
It does this by expertly switching between two key phases of its life cycle.
During the initial round of infection,
herpesviruses are very active in what is known as a lytic infection.
Here the virus is using all of its genes to hijack
the host cell's machinery and produce a horde of new virus particles.
These can be neatly packaged up and released from cells,
or the cells can burst open Alien-style and let loose their infectious passengers.
Either way, the goal is clear: go forth and multiply.
But in order to remain a silent, lifelong infection,
evading an immune system which seeks to destroy it,
the virus has to get really sneaky, entering a prolonged period called latency.
Unlike the lytic infection, when the virus is incredibly active,
very few genes are expressed during latency.
But what few genes remain switched on can still achieve a lot.
They keep the virus alive, make sure the virus is passed on when cells divide.
But even more importantly, they act to tamp down other viral genes,
making the virus nearly undetectable to our immune system.
For most people infected with EBV, once the virus enters latency,
that’s the last they’ll hear from it.
But for an unlucky few, generally those who are immunocompromised,
it comes back with a vengeance, reactivating its genes
and re-emerging with the same nasty symptoms.
But when you get mono again, it's still mono.
So why does shingles get to be special?
Well, it starts a lot like EBV.
Chickenpox is caused by the varicella-zoster virus, or VZV.
Though we’re not sure of the mechanism yet, it’s believed that the highly infectious
VZV enters your body through the respiratory tract,
where it makes its way to infect the T cells of the immune system.
The T cells then go about their usual business,
circulating in the blood where they unknowingly deliver the virus to your skin.
Here, the virus causes the skin to break out in itchy, fluid-filled blisters.
While your body is fighting the infection on one front in your immune cells and skin,
the virus is sneaking behind enemy lines and setting up camp and entering latency
in your peripheral nervous system, in clusters of nerve cells known as ganglia.
The peripheral nervous system sends information all over your body.
That’s why the symptoms of shingles can break out almost anywhere.
We don’t understand exactly how VZV hunkers down during this decades-long
latency, but it relies on changing which viral genes get read out and put to use.
One way is by switching on one of its genes called ORF63.
ORF63 has been found to protect human neurons against apoptosis,
often defined as programmed cell death, which is used to eliminate harmful cells.
If a cell is damaged or infected with a virus or just old,
the cell can say “the needs of the many outweigh the needs of the few”
and pull a Mr. Spock to protect the rest of the body.
By putting a hold on the normal cell death that comes with aging,
the virus can comfortably live out its lazy latency days in a cozy neuronal home.
VZV also uses another gene called ORF61 to maintain latency, but with a twist.
During its busy, replicating lytic infection, ORF61 encourages
the virus’s genes to be used at a greater rate.
It increases the production of mRNA from those genes,
which means they’re getting read and turned into proteins more often.
Which makes ORF61 pretty important for
the virus’s replication during an active infection.
This master of replication is still being produced by
the hijacked neurons during latency, but it has an evil twin.
Almost literally. The ORF61 gene starts getting read
backwards as well as forwards.
Because of how base pairing works in nucleic acids,
that means the backwards mRNA pairs with and sticks to the frontwards mRNA.
The backwards version gets produced 5 to 9 times more than its counterpart,
at least based on what we know from animal models.
That means it totally swamps the frontwards version
and prevents it from being made into a protein.
That, in turn, puts a hold on viral replication and
keeps the virus hidden from the immune system.
There’s even more going on that we don’t totally understand yet.
But it’s clear that VZV is using clever genetic tactics to keep itself deep undercover
in our neurons, biding its time until it just… switches back on again.
Because in about one third of adults who have been infected
and haven’t had the shingles vaccine, it will switch back on.
Gene expression ramps back up, and the virus begins to replicate again.
New viral particles travel down the axons, or long stems,
of the neurons they’ve been living in.
Then the particles are released, causing painful lesions
in the areas of skin the neurons connect to.
And presto: shingles.
Even after the blisters fade, patients may
continue to experience chronic nerve pain.
So that is why chickenpox feels so different from shingles,
despite being the same virus.
One begins life in your immune cells, and the other in your neurons.
This is unlike EBV, which infects and remains dormant in the same immune cells
throughout its life, coming back around as a fresh case of mono.
We still don’t know exactly how and why VZV knows to rear its ugly head again,
but the fact that shingles is most likely to occur in the elderly gives us a clue.
The decline of your immune system with age may give VZV the perfect opportunity
to spread more successfully than the first time around,
now that your body is lacking its viral defense system.
That’s why the CDC recommends the shingles vaccine for people
who are 50 or older, or people who are immunocompromised.
Now, if they’re caused by the same virus,
it might seem odd that we have different vaccines for chickenpox and shingles.
Unlike the chickenpox vaccine, which uses a whole but weakened form of VZV
to build immunity, the shingles vaccine Shingrix contains
just a single protein found on the outside of the virus.
This means it can be administered to people with weakened immune systems,
but is still enough for your immune system to know
what to attack when VZV crops up again.
There is also another shingles vaccine that’s a live, weakened version of the virus.
But we still keep them separate for safety reasons,
since they were tested on totally different groups of patients.
Ultimately, the vaccines work in a pretty similar way, and right now it looks like kids
who have had the chickenpox vaccine are a lot less likely to get shingles later on.
But as the first large group of people to get the chickenpox vaccine got it in 1995,
they’re still relatively young, so that’s definitely a thing
we’ll still be finding out for a while.
The protection of a vaccine decreases the odds that VZV
will come back around as a whole new illness.
Although shingles won’t happen to everyone who’s had chickenpox, it can;
as long as that virus is hanging out, it could come back.
Herpesviruses: the gift that keeps on giving.
Like the last guest at a dinner party, VZV refuses to leave even after
our immune system has asked nicely, just hiding out in a different room
of the house and remaining undetected until it
finds the perfect moment to strike again, less welcome than ever.
This SciShow video is supported by Brilliant.
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