The Aftermath of Viruses – Episode Transcript

INTRO:

MAIKEN SCOTT: This is The Pulse — stories about the people and places at the heart of health and science. I’m Maiken Scott.

Viruses on their own are pretty much helpless.

CAROLINA LOPEZ: They are 100 percent dependent on infecting cells.

MS: This is Carolina Lopez — she is an immunologist at Washington University School of Medicine in St. Louis.

CL: They cannot go anywhere. They basically can’t replicate. Outside a cell they would just disappear.

MS: Viruses are dependent — but they are sneaky. They get into cells, and use their infrastructure to replicate, to infect another cell, and another one.

CL: … Amplify themselves and multiply themselves, always using and taking advantage. They’re like parasites.

MS: Are they alive?

CL: That’s a really good question. Well, what defines something being alive? I don’t know. I think they are really good at taking advantage of live things to keep propagating. But since they’re completely dependent, I think there’s aspects of the definition of life that may- may not apply to viruses.

MS: So, they may not be fully alive, but like zombies, they can also be really hard to fully kill. To get rid of the virus, the immune system has to kill infected cells, but Carolina says many viruses find ways to hide.

CL: For a lot of viruses we know, a lot larger, more complex viruses, we know that they have a strategy to stay, that allows them to hide the infected cells from this immune response for example. So, this infected cell is not seen. And then if you don’t eliminate it, kill it, clear it, then you will have that virus always hanging around in your body.

MS: Sticking around, in any way possible…

CL: And we’re finding, with more sophisticated tools, just not looking for actually fully competent viruses, but looking for elements of the virus. It’s genetic material. Maybe it’s proteins. If we go and look for those little pieces of the virus in the body, we’re starting to find that a lot of these viruses actually are maintained for a long time in in the body.

MS: Waiting for a chance…

CL: What we call reactivate and actually pull these pieces together and make another virus that could re-infect new cells eventually.

MS: It almost sounds like it’s an enemy that you’ve beaten back, but then the enemy is just waiting to regroup and at the right moment will attack again.

CL: Yes, yes, because they’re so dependent on being in bodies, in our bodies, they need to find strategies to escape the immune response. I think we’re at the point of being pretty convinced that they stay a lot longer with us, than we thought initially.

MS: This has certainly come into sharper focus during the pandemic — there are thousands of people who had COVID-19, got through it — thought they were fine — but then realized, this virus was not done.

MONTAGE: I began to feel like somebody was taking a vacuum cleaner and sucking the life out of me. I just started to just melt, like, just just melt. Everything started to change.

And this fatigue just unbearable. Lifting up my cell phone to just look at the time was exhausting.

That’s when we started to realize that we might have a problem, with the covid being gone, but not gone?

MS: Gone, but not gone. On today’s episode: viruses — their impact on our bodies, and what happens when they stick around.

MUSIC

SEGMENT 1:

First up: let’s take a look at the people who are experiencing long-lasting symptoms from coronavirus. Here’s one woman’s story, she first got sick last year.

MELANIE MONTAÑO: My name is Melanie Montaño. I’m 33 years old and I’m a writer. Honestly, I have never been more aware of a calendar date than March 15th. March 15th was the day I woke up and I had a low grade fever. It was a ridiculously uncomfortable and unfamiliar level within my own body, there was extreme labored breathing. I had this violent coughing fit that just would not it would just not ebb … almost what feels like lava coated lungs and trachea. It was just this intense heat that radiated throughout my trachea and my lungs. Nothing I’ve ever experienced before.

I had lost my sense of smell and my sense of taste. And the list goes on. And these symptoms, essentially, they came and left and came and left in this cyclical pattern for about three months.

It was really, it was, it’s odd being kind of trapped in your own body and you feel like there’s a host, essentially, that you’re just you’re kind of accommodating it without knowing what the next day is going to bring. It was really daunting and terrifying.

MS: The weeks and months dragged on, and the unwanted guest in Melanie’s body kept making its presence known, in ever changing ways.

MM: I have not been the same ever since. I’m now facing a slew of other complications because of it. So I will say, you know, the labored breathing a little bit, subsided a little bit. But the fatigue is still there. A new development of brain fog emerged. And essentially I’m still rendered pretty useless at this point. And we’re talking about one year after the fact. It’s just something in which you wake up and you don’t know what to expect.

MS: That’s Melanie Montano – she’s living with ongoing issues from COVID-19.

I wanted to talk to a physician who is treating people like Melanie — and I reached out to internist Neda Frayha. She’s a primary care doctor in Maryland.

MS: Neda, let’s start with the name. What do we call this thing?

NEDA FRAYHA: Most people think of it as “long COVID,” some people refer to it as “chronic COVID” when the symptoms related to the COVID infection or other symptoms have gone on, past 12 weeks. Actually, just recently, in late February, Dr. Fauci announced that the National Institutes of Health is going to study this syndrome. And there they introduced a new name called Post Acute Sequelae of SARS-CoV-2 or PASC. There are lots of names — I think most of us tend to say long covid and people within the community that are suffering from all of these symptoms refer to themselves as long haulers.

MS; Now, as a physician, what has to be present for you to make this diagnosis, or is that still emerging?

NF: It’s really still emerging. Right now, if a person had a COVID infection, and now some number of weeks to months later, they’re still not themselves. They are suffering from horrible fatigue or they’re having shortness of breath or they have what they call brain fog or they’ve got muscle aches all over. If they have long-lasting symptoms that go beyond the short-term infection, that’s enough. That’s enough for us to think of them as having long COVID.

MS: So right now, lots of people are focusing on the light at the end of the tunnel with this pandemic — people getting vaccinated, finally hugging their parents, grandparents, maybe even planning a vacation — but for many, the virus is with them every single day, with no answers or relief in sight.

NF: You know, when you hear their stories, it’s incredibly humbling. Many of the people I know in my practice and my panel of patients, even among my friends who had COVID and then have long lasting symptoms afterwards, they’re healthy, they’re young. Many of them are in their 30s to maybe early 40s. Many of them were completely healthy before they got COVID.

And now they say they used to be able to do spin classes and run half marathons. And now just trying to walk their dog around the block leaves them completely winded and unable to breathe. Another example is walking up a flight of stairs can cause one person’s heart to raise up to 150 or even 200 beats per minute, just walking up a flight of stairs. And this is someone who could exercise a lot before she got sick. So these are just small examples. What I hear over and over again over time is that when they try to go back to work, they find that they can barely make it through a few hours of their normal workday before they are just completely depleted of all their energy. They just want to face-plant onto their bed and stay there for days because they have no energy.

MS: That happened to Angela Aston — she is a nurse in Central Texas. She had coronavirus in March of 2020, and continued to have symptoms. After two months of this, she was desperate to get her life back.

ANGELA ASTON: I went back to work one day and I didn’t feel like I was ready to go back to work. But you’re supposed to be better. So I was like, OK, I’m going to go back to work. And I still felt unsure of myself — I felt weak, I felt confused, I just didn’t feel right, but I’m like, ‘OK, I’m a hard worker, I’m going to go back to work.’ And I went back to work. I probably made it til noon. And then I started having, like, shortness of breath and I was having heart racing and I think I had a panic attack. I ended up that night at an emergency room. I left work and didn’t go back to work until July.

MS: Neda says a lot of her patients just want to feel like themselves again.

NF: And I think it tests a person’s patience, that tests a person’s sanity sometimes. The overarching theme that all of these people tell me is I just want to get better. I want to get back to my normal life. I want to take care of my kids. I want to go to my job. And they just are really debilitated by the fatigue, the muscle pains, the trouble breathing. One friend told me that she kept thinking she could feel better if she just drank more coffee. She’s like, ‘oh, I’ve been tired before, I’m just going to drink more coffee,’ and not only did it not help, but then she was completely jittery from all the caffeine as well. So it’s really quite miserable and quite humbling.

MS: What do you do for them? I mean, it sounds like this is too new to really have tried and true treatments for this. So what do you offer people?

NF: I think there are two really important things that we in the medical community can offer until we know more — until we have, you know, a gold standard treatment for long COVID or PASC. I think one thing we can offer is just validation and letting our patients know, I hear you. I believe you.

The second thing that we can do is to take a really good look at what specific symptoms does the person have, and to try to come up with a good plan based on those symptoms. So if someone has really terrible trouble breathing, they just cannot take in a deep breath or they can’t walk more than five feet before becoming completely winded, then I’m going to work that up, make sure there’s nothing more serious going on underneath the surface and try to give them treatment to help that symptom. Same thing for if we’re talking about muscle aches, same thing for if we’re talking about insomnia, depression, anxiety and so forth.

MS: Neda told me doctors are talking about this a lot — exchanging info and tips, texting each other

NF: What are you seeing? What are you finding? What’s been helpful?

MS: But so far, they’re pretty much operating in the dark, what they know is based on observations.

MS: How much research has been done already and what have those studies been about?

NF: There have been a handful of smaller studies and by that I mean looking at a couple of hundred patients each. There have been, interestingly, some radiology studies looking at how long it takes the signs of lung damage on the CAT scans to get better. And there we see that within a few months. So maybe two to three months, you can see some real improvement in how the lungs look on CAT scan. And so sometimes I use that just to try to give my patients a sense of when they might start to hopefully breathe more easily, that most of the time people tend to have improvement within two to three months, for example.

There are some reports that people who have long covid actually start to feel better physically when they get the covid vaccine. And it’s beyond just the sort of mental relief of it. It’s an actual physical improvement in their symptoms when they’re vaccinated. But this is something that anecdotally a lot of clinicians are sharing with each other, like, hey, this is happening with my patients. Hey, me too. And now there have been a couple of mentions about it in the Lay Press. So just something really interesting for us to keep an eye on.

MS: Neda Frayha is an internist, and the host of the Primary Care Reviews and Perspectives podcast.

NF: Each component of that that we get an answer to will help us find a treatment that can actually help the person in front of us feel better and get back to living their normal life, get back to work, get back to caring for their families.

MS: But that could take a while, right?

NF: It could, absolutely. It could take years, at least a year.

MS: In the meantime — many patients who are dealing with these issues are trying to find a way to get through. Here’s Candice Taylor, who lives in Atlanta, Georgia.

CANDICE TAYLOR: I’m actually trying to learn the new me, you know, with chronic illness, which I believe COVID is like a chronic illness, is trying to give myself grace not to get frustrated when my heart rate is 140 beats or I’m dizzy or I can’t think of a complete sentence because I’m having brain fog that day. So it’s just learning to accept the new me, I guess, the person I’m becoming just because I’m not the same as far as activity wise, I can’t you know function like I will usually wake up early in the morning and go, and now it’s like I’m barely getting out of bed and so is learning to navigate through what I was once in 2020 into 2021. I have hope that the medical community and science will catch up. Not just for long haulers or long COVID patients, but people with chronic illnesses, because we need assistance and you know we need help.

MS: That’s Candice Taylor of Atlanta, Georgia, who’s been dealing with symptoms related to covid-19 for more than a year.

PROMO:

We’re talking about viruses, and what happens when they seem to stick around in our bodies — and continue to affect us.

Coming up — could studying long-haulers finally bring some answers to medical mysteries?

Leonard Jason: unexplained illnesses, um, are, as these things are unfortunately, um, really consume a lot of healthcare dollars. So a lot of people go to physicians, um, something like 20, 25% of visits are for things like, um, pain and fatigue, many cases unexplained

That’s next on The Pulse.

SEGMENT 2:

MS: This is The Pulse — I’m Maiken Scott. We’re talking about viruses, and what happens when they stick around.

Immunologist Carolina Lopez got fascinated with viruses because they are simultaneously mighty, and powerless.

CL: It always intrigued me, how these minimal, you know, capacity entities were able to do so much damage. To cause disease and kill people being so, so small and powerless compared to our own bodies and our own defense systems.

MS: And what makes a virus, a virus? What do they all have in common?

CL: That’s a fantastic question. I wish we had a real, really, really good answer. But in general, I would say these are they have to have our genetic material, so they have to encode for minimal information that will allow them to propagate. So they usually have just the capacity to code for very, very few minimal proteins that are needed to that to work together with proteins from their cells they are infecting to to make them replicate and propagate

MS: So how many different viruses do we know about, just roughly?

CL: Oh, I don’t know. I mean, I mean we have tons of viruses, different species, which means, you know, made of different things, different kinds of genetic material, capable of in fact different any sort of life thing, millions and millions of different viruses. And actually our bodies have a lot of viruses.

MS: Viruses can be really good at getting around our defense systems. They can hide in our bodies in one shape or another. One example is the varicella-zoster virus — it’s the very contagious virus that causes chickenpox. I had that as a kid — an itchy rash and fever, and then, that same virus brought me a case of the shingles, decades later! I asked Carolina how that virus manages to attack again

CL: So that is one of those examples of large viruses that have developed a lot of strategies to keep themselves alive, persistently infecting. So, in the case of chickenpox, the virus actually goes and leaves in neurons and in the skin cells that are relatively long-lived.

So, for example, neurons, they you don’t want to kill your neurons. This cell type is a cell type that is at limited numbers in our body and plays very important roles. So the virus, a virus living there is actually a very good way to hide from our immune system. And again, these viruses, because they are large, they have a strategy. So they have proteins that work in, you know, hiding it from actively hiding it from the immune system. It changes the way the cell is seen by the immune system. So they evade the immune response, for example.

MS: I wanted to ask about long haulers who have been dealing with months and months of symptoms, sometimes after a pretty mild initial case of COVID-19. What are we finding out about that virus, sticking around?

CL: Yeah, I think the key evidence is accumulating to very clearly show that there are remnants of the virus in the body of these patients. There is a recent publication that actually showed viral proteins in the gut in the GI tract of these long COVID patients. It could be that it hides in the brain. For example, the brain is another place where you don’t want your immune system to attack it. So it’s usually a very good strategic place for viruses to go on, to stay there, you know, quietly until they can come back and do what they do.

MS: Finding out how viruses stick around long-term, or hide is tricky to study. For example, Carolina is interested in respiratory viruses that potentially have a link to asthma later. But if you want to learn about the long-term impact of a virus, you first have to figure out how to keep a virus around.

CL: So the first thing you need to have is a way to grow and maintain the virus alive in the lab. Right. So some viruses are a little harder. Some viruses need things that we may still don’t know what they are in the body. So it’s very hard to reproduce their life cycle, let’s say, in the laboratory or in animal models. And that limits enormously what we can do.

MS: Viruses need cells to infect — and I mean, don’t want to anthropomorphize them but they sound like they’re very picky.

CL: You need to find cells of the virus like so if the virus doesn’t want to infect your cell. Well, it’s not going to go in. So the first hurdle is having the cell that the virus like and making that interaction possible. So then the virus can go into a cell, multiply, and then you can study the virus in amounts that are, you know, useful.

MS: Could this whole pandemic change some of the fundamental thinking in your field? To study some of the things that can happen after a virus attacks?

CL: Yeah, I think it will definitely change the priorities, I would say, and also the focus of many of our labs. I mean, this is not the first time that we know that these viruses that we consider very acute seems to stay longer. Right. And we have a recent example with Zika, and we know that they persist or the effects of the infection persist for a long time. I don’t think it has being an equally, you know, effort. Right. From the scientific community. In follow up on those, there are a number of lives that have been studying these persistent viruses for a while. But I definitely think we need to do a lot more because once the virus passes, I mean, it’s not only the symptoms, right. But we need to to ask ourselves what else it happens to that person. If another virus come right, it is make them more susceptible and less susceptible, for example, to a second infection with a virus or a bacteria or et cetera. So there’s a number a number of aspects that that these persistent viruses could be influencing. And we really haven’t paid enough enough attention.

MS: That’s immunologist Carolina Lopez. Chances are, the pandemic will bring an infusion of research dollars to study how viruses can affect us in the long run. This may finally shed some light on some other potentially post-viral conditions that plague lots of people.

Jad Sleiman has this look:

JAD SLEIMAN: Psychologist Leonard Jason knew the COVID long-haulers were coming long before anyone even had a name for them.

JASON LEONARD: When we began hearing about individuals getting sick with this particular virus, we just assumed that there would be a certain percentage of individuals who did not recover and they ended up calling them long haulers.

JS: He directs the Center for Community Research at Depaul University in Chicago. He tells me it was no surprise some subset of those infected just stayed sick because that kind of thing has always happened.

JL: So if you look at all the different viruses that have occurred from the Spanish flu 1918 to Ebola, um, to SIRS, a certain percentage of people don’t recover, and that’s what we’re interested in. Why is it that some people don’t recover from a wide different host of viruses that have occurred over the last hundred years?

JS: Leonard works with a community suffering from a disease many experts believe has a viral trigger. It’s a baffling condition with a wide range of symptoms.

KIM CARLSON: The fatigue is profound. It’s like wearing a suit of armor and the floor is a magnet.

JS: That’s Kim Carlson of Minneapolis.

JUSTIN BLONSTEIN: Brain fog, where it’s tough to put thoughts together. It kind of felt like the flu without the stomach ache.

JS: Justin Blonstein of California.

ANN MCDONALD: It’s like being held to your bed with invisible straps, day in and day out.

JS: And Ann McDonald of St. Louis.

They all were diagnosed with chronic fatigue syndrome. It’s characterized by this relentless tiredness. This disease is also commonly known as myalgic encephalomyelitis so we’ll call it, ‘ME/CFS.’ Here’s Ann again:

AM: Having ME/CFS is like straining to walk through the deep end of the pool. When you’re simply trying to get from your bed to the bathroom.

JS: And Kim says you gotta be vigilant.

KC: One of the most difficult aspects of daily life is monitoring how much gas I have in my tank as far as my energy reserves and trying not to overdo.

JS: If someone with this condition is too active for too long, they’ll crash hard and find themselves bed bound.

KC: I even wear a Fitbit to take as few steps I can take in a day.

JS: ME/CFS has long been linked to the Epstein Barr Virus which causes mono. But there’s no concrete test for ME/CFS, and there are dozens of other suspected causes. That speaks to maybe one of the toughest parts of having this disease — not being taken seriously.

AM: Being Dismissed from doctors is soul crushing

JB: It can be very frustrating because it’s been shoulder shrugs more than anything else.

JS: That disbelief is how Leonard — who, remember, is a psychologist — got involved with this community. When physicians don’t know what to do for a patient, they’ll sometimes suggest therapy. Back in the day, instead of calling it Chronic Fatigue Syndrome or ME this condition was sometimes called Yuppie Flu. As in, made-up nonsense.

JL: It’s easy for, you know, the healthcare worker to say, well, you know, maybe you’re just depressed. Maybe, you know, you just need to sleep better and you’ll get over this. And, and why not just take this antidepressant?

JS: That attitude is part of the reason this condition got so little official attention.

JL: In 1991, myself and Judy Richmond, who’s a sociologist at the University of Illinois, Chicago, we sort of marveled at the fact that there were so few people identified with this illness by the CDC at the time.

JS: The Centers For Disease Control thought there were maybe 20,000 people with this disease in the United States. But at the time, just one major ME/CFS support organization had more active members than that.

JL: And also three to 4,000 people every month were calling the CDC with- trying to get information about this type of fatiguing illness. So we thought that their estimate of less than 20,000 people was an underestimate.

JS: Which is a bit of an understatement.

Leonard and his colleagues wanted to get a sense of the true prevalence. They screened a random sample of thousands of people from diverse ethnic and socio-economic backgrounds, mostly over the phone.

From that work they estimated the true number to be around 1 to 1.5 million. Women were two to four times more likely to be diagnosed.

JL: And by the way, it turns out that individuals of color, Black and individuals who are Latinx actually are higher rates.

JS: Medicine doesn’t really understand this disease, yet. But that doesn’t make it any less real for those who have it.

JL: If you’ve got multiple different reasons for a person seeming to get sick, in some cases, they can’t find any reason. They just slowly got worse over time, and then it’s harder to attribute it to something specific.

JS: Leonard and his colleagues think some kind of attack on the brain is what causes ME/CFS.

In the case of viral infection, they think it could be linked to what’s known as a cytokine storm. You may have heard of it in COVID patients. It’s basically an over reaction of the immune system that can start to damage and destroy tissues, causing harmful swelling — sometimes in the brain.

But It may be the case that ME/CFS, or at least some cases of it, could also be caused by something else, something that isn’t on anyone’s radar.

JL: Unexplained illnesses are, as these things are unfortunately, really consume a lot of healthcare dollars. And I don’t know if you know, about 80% of lower back pain is unexplained. So a lot of people go to physicians, something like 20-25% of visits are for things like, pain and fatigue, many cases unexplained.

JS: Hard to explain medical problems, he says, can often become easy to dismiss medical problems. That’s especially true when the weird cases trickle in here and there.

These people were invisible to the larger health care community one, because their symptoms were so strange and varied. And two because there wasn’t one big cause that could tie all these patients together.

Now, with the pandemic, millions of people are getting the same virus, thousands of them are staying sick — and it’s happening all at once. Leonard thinks that makes for a more clear pattern, one that’s hard to ignore.

JL: With COVID-19 you can see a very different case where, you know, that people had this particular illness and they got sick after it. Well, with ME/CFS, you didn’t have everybody have like a virus, um, like COVID that basically had an insult to their system of which they didn’t recover

JS: The pandemic and it’s sudden onslaught of strange long-haulers unable to smell, out of breath for months on end, may force a change. They’ve ignited renewed investment in research that could end up helping those with ME/CFS. But Leonard tells me the sheer visibility of long haulers is invaluable.

JL: I think the fact, there’s so many thousands, hundreds of thousands of people who are sick, who have had, you know, stellar careers and, and they want to basically figure out what’s wrong. You have, that whole group that is, you know, basically trying to get their voice heard. They won’t be silenced.

JS: For those long suffering COVID longhaulers, there may be some comfort in knowing that they’ve joined a community of people in those with ME/CFS. A community that they maybe didn’t know existed. Both parties less alone and a little louder post pandemic.

For the Pulse, Jad Sleiman.

MS: You’re listening to The Pulse, I’m Maiken Scott — you subscribe to our show wherever you get your podcasts.

I asked immunologist Carolina Lopez – what more research on these issues would actually mean for people who have illnesses that are probably post-viral in nature…

MS: If we were to make that connection. And we could say when you have this virus sort of hiding out in your body, it can lead to this, this and the other thing, would that mean that we could do anything about it?

CL: That’s why it’s important that we as a scientific community start studying it. Right. Because if we understand where the viruses persist, for example, and we can devise a strategy to eliminate that reservoir, or what are the factors that make a virus go in this kind of dormant or under the radar stage. And we can manipulate those factors. So the more we learn about how these interaction occurs and what is the consequence, where the virus is, et cetera, the more we can think on strategies to potentially eliminate them or suppress their ability to reactivate whenever these viruses reactivate. And we need to put effort in investigating all that, because it clearly can highlight opportunities for us to intervene and avoid these reactivations and whatever disease they may cost.

Carolina Lopez is an immunologist at Washington University School of Medicine in St. Louis.

PROMO

Coming up…viruses use our cells all the time – and every now and then, that can work out in our favor…

We’ll hear about one surprising example

PROMO: This virus didn’t kill the baby… if it had, we wouldn’t be sitting here as humans telling this story. What it did do, was give this offspring a premium feature

Kelsey Coolahan: We got an upgrade. Viral status.

That’s next on The Pulse.

SEGMENT 3

MS: This is The Pulse — I’m Maiken Scott.

We’re talking about viruses, and their impact on our bodies.

We’re surrounded by viruses all the time, they live inside of us — and not all of them make us sick. Some of them may actually play a beneficial role in our system. I talked about that with researcher Eric Delwart who studies viruses at Vitalant Research Institute in San Francisco.

ERIC DELWART: So it’s been shown that if you raise mice in a totally sterile environment if you prevent its gut from being colonized with the usual microbiome which is mostly sort of a complex mixture of bacteria they do not develop properly they immune system don’t develop their gut don’t develop properly and of course you can introduce a microbiome and help that animal develop but you could also replace those bacteria by a viral infection which will help to get an immune system developed so it seems you need some kind of stimulation of the immune system very young to get the whole system rolling and proper developments. There may also be beneficial viruses in the sense that it can be oncolytic – they can actually replicate preferentially in tumor cells and some companies are developing these viruses as therapies for cancers

MS: So just like a virus might attack my immune system in this case that virus would be attacking cancer cells in my body?

ED: Exactly viruses in general like to attack or replicate in cells that are dividing it provides a good milyar for their little machinery’s to make copies of itself just like HIV likes to divide in T-cells and immune system other viruses prefer certain cancer cells So what companies are developing or engineered viruses or natural animal viruses that are extremely specific for cancer cells while leaving the rest of the body of touched and these therapies which are making good progress in clinical trials would be the equivalent of a one shot therapy for cancer.

MS: That’s Eric Delwart. He studies viruses at Vitalant Research Institute in San Francisco.

And viruses are already being used in some cancer treatments – for example, herpes viruses are used to attack melanoma.

MUSIC

MS: Viruses depend on living things and —it sounds like to some extent — living things depend on them. But you can’t help but wonder, given all the damage they can do, why are they here? I asked immunologist Carolina Lopez.

MS: From an evolutionary perspective, what was the function of viruses or do we have any thought in terms of like, oh, why did they why are they here? What’s their role and how did they get to be here?

CL: That’s a wonderful question. You’re hitting the hard, hard questions seem to feel right. I don’t think we know. But what we do know is that, you know, even our own bodies and our own functions have somehow been shaped by viruses, write virus infections and viruses that have integrated in our own genome. So they just, I don’t know why they are here. I don’t know that they will have any sort of particular goal except to keep propagating and going to the next host. And in that process, sometimes, actually we have adopted them and managed to take advantage of the little, you know, you know, different activities or functions that they may be able to provide that are beneficial for higher level organisms.

MS: Our last story looks at one example of a beneficial relationship with a virus that forever changed how humans procreate. Pulse contributor Avir Mitra — an emergency room physician — reported this story with the help of a friend, Kelsey Coolahan. Kelsey is just about to graduate from Cooper Medical School in New Jersey.

KELSEY COOLAHAN: So I’m in the labor and delivery room and I’m witnessing this whole miracle of birth thing, you know, whatever, whatever. The baby is born, it’s amazing. And then you have one lonely resident at the foot of the bed who is still like slowly pulling something out of mom’s uterus. He pulls it out, he inspects it really quick, and then slaps it on the table, turns his back because he’s got more important things to deal with. But I didn’t turn my back. And I could not stop looking at this thing and just wondering like what really is this thing?

AVIR MITRA: That thing was the placenta.

KC: And it looks almost like if a pancake was made out of meat and it’s got this purple hue to it. It looks like it should be pulsating because it looks like it landed here from another planet.

AM: If you picture a baby in the womb, it’s sitting in a thin sac filled with amniotic fluid. The sac is made by the baby, not the mom. One part of that sac thickens and basically attaches to the mother’s womb. That thicker part is the placenta.

For whatever reason, this placenta needed some further inspection in the pathology lab. Most people would have followed the baby, but Kelsey decided to follow the placenta.

KC: I think something is wrong with me [laughter].

AM: That’s where she met Dr. Barroeta.

JULIETTA BARROETA: My name is Julietta Barroeta. I’m a pathologist at Cooper University Hospital. I have a subspecialty in Gynecological Pathology so part of my daily work is to look at placentas under the microscope.

KC: Yeah and that’s where I started to realize the placenta was even more interesting than it looked.

AM: Well, how so?

KC: First of all, it’s the only temporary organ. Second, it’s the baby’s lung, it’s a waste disposal system and it’s a nutrition source. Like, that’s amazing.

AM: True, okay.

KC: Everyone thinks the umbilical cord connects baby and mom, but actually, it connects baby and placenta. The placenta is in control.

AM: In order for the placenta to do all this amazing stuff, it has to do something that no other tissue can do. Julietta explains it like this:

JB: The placenta is essentially a fascinating organ because it allows for two human beings that are genetically very different. Because half of the fetus is maternal but the other half is paternal. And yet the pregnancy can go on for nine months without the mom’s body destroying it. And that, from an immune standpoint, is fascinating, because if you were to receive a piece of someone else and insert that under your skin, that would not last there for three days, your body will actively reject it.

AM: So the placenta has to be the most incredible gatekeeper. It has to let oxygen and nutrients get to the baby, it has to let carbon dioxide and waste get out. Medicines can get through, protective antibodies can get through. But if the mother and baby ever actually touched, or if any blood got through, the mother’s immune system would immediately kill the baby.

KC: So I went home and started researching. Like, where did this thing come from?

AM: She stumbled across a paper by Ed Chuong who researches molecular cellular developmental biology at Biofrontiers Institute in Colorado.

ED CHUONG: Basically, the placenta that we think of as a defining characteristic of live bearing mammals, primates rodents, dogs, cats, etc.

KC: It’s estimated that it evolved about 150 to 200 million years ago.

AM: So before that, what were we doing exactly?

KC: If you wanted to reproduce, you had to lay eggs.

AM: So before placentas, a baby had to be in an eggshell. Literally walled off from the mom.

KC: All the nutrients the baby needed had to already be in the egg from the get go. If you think about a chicken egg — that’s exactly what the yolk is, it’s a care package that has to last the embryo till it’s born.

EC: The evolution of placenta essentially involved losing that eggshell and instead replacing that with some sort of tissue or organ that attaches to the mother’s uterus during development.

AM: But losing that shell presents some challenges.

EC: At the same time it’s important that the maternal and fetal blood streams remain separate. And so the separation of these bloodstreams is established through this cell layer called the syncytiotrophoblast.

AM: The syncytiotrophoblast is the outermost layer of the placenta, the part that is pressed against the mom’s uterus. It’s literally a layer of cells that have fused together, forming a wall.

KC: This is where the magic happens. This wall of cells keeps mom and baby working in harmony and not killing each other. There’s no other structure like this anywhere else in the body.

AM: When evolutionary biologists like Ed Chuong mapped the genomes of these cells, they found something very odd.

KC: The protein that allowed these cells to fuse into a wall, it’s called syncytin, it didn’t look like it came from human DNA.

AM: What did it look like?

KC: It looked more like, drumroll please, HIV.

AM: What??!

KC: What Ed Chuong told me is that this protein actually came from an ancient retrovirus — quite similar to HIV.

AM: So you’re saying our placentas are made, at least kinda partially made, from viral DNA?

KC: Exactly!

AM: Let’s take a step back — viruses are little strips of biologic information that can’t do anything on their own. So they enter cells and hijack the cell’s machinery to make copies of themselves and replicate and move on to infect other cells. Retroviruses take it to the next level because they are strips of DNA that enter cells and just go ahead and insert themselves into the host’s own DNA. Now the host is stuck with viral DNA for the rest of its life and it can never stop doing what the virus wants.

EC: You know, today the most famous retrovirus is of course HIV, but retroviruses like HIV have been infecting vertebrates for probably a couple hundred million years.

KC: So the consensus according to evolutionary biologists, once upon a time, some retrovirus infected an egg laying vertebrate. And by chance, that virus settled into that animal’s egg cells.

AM: And it just so happened that that particular infected egg met a nice sperm, got fertilized.

KC: The baby that was hatched – whatever kind of proto-mammal it was – now had copies of that virus’ DNA in all of its cells.

AM: Right because if the retrovirus managed to insert itself into that first cell, it would be copied into every subsequent cell.

KC: Yup.

AM: This virus didn’t kill the baby… if it had, we wouldn’t be sitting here as humans telling this story. What it did do, was give this offspring a premium feature

KC: We got an upgrade. Viral status. Viruses fuse with things in order to infect them. So now, we get this viral DNA that lets us make a protein that … fuses things.

EC: Once a viral protein, it essentially morphed or evolved into what we now know as syncytin.

KC: So, back to the proto-mammal. It contains viral DNA that codes for this syncytin protein. This protein gives the baby the ability to fuse cells into a wall. A wall that connects mom and baby but also keeps them separate.

AM: It gives this baby the ability to create a placenta.

EC: Basically this virus helped that mammalian ancestor survive better by giving it a better placenta, then this piece of DNA would have been passed on to the generation and eventually spread into the population. And this process we think of as a molecular domestication of an ancient retrovirus.

AM: Wow. So the virus tried to hijack us, but we hijacked it.

KC: It’s worth noting that this probably didn’t happen overnight. This was the key step, but it probably took many more generations worth of mutations.

AM: But still… talk about turning lemons into lemonade.

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AM: It’s not just placentas — biologists have found huge chunks of our DNA that are actually remnants of ancient viral infections. Looks like we’ve been domesticating viruses for a long time. Or have viruses been domesticating us? Either way, what all that DNA is doing for us, for the most part is still a mystery.

KC: It just seems like in a way we’re part virus, otherwise we’d be laying eggs.

EC: Exactly, I think that is the key takeaway [laughter].

MS: That story was reported by Avir Mitra, and Kelsey Coolahan. Avir is an emergency room physician in New York City and Kelsey is just about to graduate from Cooper Medical School in New Jersey.

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That’s our show for this week — The Pulse is a production of WHYY in Philadelphia.
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Our health and science reporters are Alan Yu, Liz Tung, and Jad Sleiman. Sojourner Ahebee is our health equity fellow. Charlie Kaier is our engineer. Xavier Lopez is our associate producer. Lindsay Lazarski is our producer.

I’m Maiken Scott, thank you for listening!