Last week brought the horrifying news that the Ebola virus can live in the eyeballs of survivors, even after it’s been eliminated from the rest of the body. It shouldn’t have been a surprise, though. Viruses have always hidden in parts of our bodies you’d never expect. In fact, we’re all walking virus reservoirs.
It’s not just rare diseases like Ebola. Ever had chickenpox? Or a cold sore? The herpesvirus that causes these two illnesses actually remains inside your nerve cells for a lifetime. They’re able to do it because your immune system can’t reach them there. Indeed, viruses generally hide by exploiting blind spots in the immune system. That means generally one of two things: 1) infecting areas of the body that aren’t entirely under the control of our immune systems or 2) going dormant inside cells so that the immune system can’t detect them.
Viruses are able to pull off these acts of subterfuge because they’re tiny and simple. They’re just short bits of genetic material—RNA or DNA—protected by a protein shell. Unlike other microbes, they cannot reproduce on their own, so they have to attack cells and hijack their protein-making machinery to replicate. Usually, our immune systems are there to fight back. But sometimes, they’re not.
Viruses stay hidden in our bodies by exploiting a vulnerability in our immune systems. This vulnerability is called “immune privilege,” and comes from an old observation that foreign tissue transplanted into certain parts of the body don’t elicit the usual immune response. This includes the brain, spinal cord, and eyes. Scientists believe this is because the brain, spinal cord, and eyes are simply too delicate and important to withstand the inflammation that’s typical of an immune response.
But these body parts—vital to our individual survival—are not totally defenseless either. The eye, which is directly exposed to the outside world, has its own immune system to fight off pathogens while limiting inflammation. The brain, for its part, has an army of cells called microglia that gobble up pathogens and damaged neurons. The blood-brain barrier, once thought to keep the normal immune system out of the brain, also turns out to be porous to certain immune cells.
So the idea of immune privilege is not as absolute as scientists once believed, but these are still areas of the body where viruses do encounter fewer patrolling immune cells. And it helps explain why Ebola can hide in eyeballs. The virus can also be found in the testes for months, because that’s another area with immune privilege.
Some viruses hide by basically playing dead inside your cells. Chickenpox and shingles, for example, are caused by the same virus, the varicella zoster virus (VZV). And yet chicken pox and shingles look very different: you get itchy red blisters all over your body with chickenpox, and isolated rashes or nerve pain with shingles. The two diseases seem entirely distinct because shingles from VZV that has gone into hiding.
As your immune system beats back VZV, the virus retreats inside your nerve cells. There, they stop hijacking the cell’s molecular machinery and they stop reproducing. Those segments of viral DNA just hang out, lying low until some trigger awakens them. Usually the trigger is some kind of stress or health disturbance. That’s when VZV mounts it attack again, spreading along nerves and causing the characteristic streaks of itchy rashes in shingles.
VZV is in the family of herpesvirus, which all have the ability to lie dormant in cells. Herpesvirus include, yes, herpes simplex virus types 1 and 2, which cause cold sores and genital herpes, but also Epstein-Barr and cytomegalovirus, which cause mono. In the case of the herpes simplex viruses, scientist have found that certain genes, called latency associated transcript (LAT), are most active when the virus is dormant. The LAT blocks the expression of genes used when the virus is active.
Other viruses, like HIV, can even seamlessly integrate their genetic material into the DNA of cells. This, as you might imagine, makes them extremely difficult to get rid of.
The short answer is, we don’t know.
In the case of immune privilege, doctors make every attempt to administer antiviral drugs that can cross the blood-brain or brain-eye barrier to neutralize the virus. The patient with Ebola in his eyeball recovered after taking an experimental antiviral drug and a course of steroids, but it’s hard to say if the drugs were responsible for killing off the virus. The immune system isn’t entirely absent from the eye, after all, so it’s possible viruses in immune-privileged areas can still be fought off naturally.
In the case of latent viruses hiding inside cells, scientists attempt to lure the viruses out of their hiding places. Herpes, for example, goes through cycles of latency and outbreaks. Researchers are studying the LAT genes that allow the virus to lie low, in hopes of figuring out a way to keep the viruses switched on. When it’s awake, the virus is easier to kill with antivirals — and it’s also possible that one day we might silence these viruses entirely by using molecular tools that neutralize the viruses’ genetic material.
One molecular tool that is getting a lot of buzz now is the CRISPR/Cas9 system, which could even directly go after viruses that have integrated into the genome. CRISPR/Cas9 is a genome editing tool that actually comes from the virus-killing immune systems of bacteria. It’s a natural-born virus killer, if you will. Scientists recently showed it could be used to cut latent HIV out of human cells.
Humans and viruses are in an arms race that has lasted tens of thousands of years, as our immune systems have evolved ever better ways to kill them — and they evolve better ways to exploit our vulnerabilities. But one day we may get out of the evolutionary feedback loop. It all depends on whether we can ever understand viruses well enough to turn their own defenses against them, shutting them down with the very genetic codes that let them hide from us right now.
Top image: Ebola budding from a cell. NIAID
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