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As a SciShow viewer, you can keep  building your STEM skills with a 30 day free trial and 20% off an annual premium  subscription at Brilliant.org/SciShow. 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. [♪ INTRO] 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.

When the kids who got the  chickenpox vaccine get older, there will undoubtedly be new data that  tells us how likely they are to get shingles; data that might be presented  in many confusing graphs. So to help you understand those graphs  when you see them, there’s Brilliant! The Brilliant course titled “Understanding Graphs” is all about how to…understand graphs.

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