ROXANNE KHAMSI: This is Science Friday. I’m Roxanne Khamsi. Throughout the pandemic, scientists have been learning more about SARS-CoV-2, the virus that causes COVID. But there are still big questions, one being how long does the virus persist? In other words, how long does it hang around in the body?

Persistence can clue us into ideas of immunity and how long people are infectious. And this is a question that researchers have about all sorts of viruses from SARS-CoV-2 to HIV to measles. My next guest is here to talk about what we know about how viruses hide out in the body and why they might do that. Diane Griffin is a Professor of Molecular Microbiology and Immunology at Johns Hopkins in Baltimore, Maryland. Welcome.

DIANE GRIFFIN: Thank you.

ROXANNE KHAMSI: So Diane, I had mentioned this idea of persistence of viruses. What does that mean? Why is this important to understand?

DIANE GRIFFIN: Well, the persistence can be in several different forms. Mostly, when we get sick with these acute kinds of infections– SARS is a good example, but the example that we’ve been studying is measles– you think that as soon as you feel better and go home that the whole infection is over. But actually, that’s not really the case, even though the infectious virus that we can actually culture and that makes you be able to give the virus to somebody else is actually usually cleared or gone very quickly after people start to feel better.

But the RNA– in this case, that’s the genome of the virus itself– actually, it takes a much longer period of time for it to be able to be cleared. And that may be actually doing something during that very long period of time that it hangs around.

ROXANNE KHAMSI: One question at the beginning of COVID was with PCR tests, which tap into some of that RNA that you’re talking about. So was that test picking up the virus itself or fragments of the virus?

DIANE GRIFFIN: Well, it’s picking up the genome, the RNA of the virus. And the test itself doesn’t really tell you whether it’s picking up the whole viral genome, which then could start replicating again, if you gave it a chance, or just a piece. So the PCR test itself does not really give you that information.

ROXANNE KHAMSI: So, I mean, it sounds like this is very new terrain because we’ve got these tests now that we can poke into this new question, but, historically, we’ve thought there’s two kinds of viruses, right– those that clear out of the body, just as you described, and once you get over the illness, the virus is gone, and then others that stick around for a lifetime, like HIV or herpes. Can you give us a basic idea of how this works, like whether a virus sticks around or not?

DIANE GRIFFIN: Yes. Well, the viruses that stick around that you’ve mentioned, like herpes and HIV, actually stick around in a form where they’re still infectious. And those viruses all have a DNA phase to their replication. So they have a mechanism for being often incorporated into the genome of the host cell so that they are not easily cleared or basically can’t be cleared.

But other viruses don’t have that same mechanism, which is the reason that we’ve been surprised that these viruses that don’t replicate or have a nuclear phase are all in the cytoplasm. They can still hang around for very long periods of time. There’s a fair amount of evidence that they’re actually at least making viral proteins because they’re stimulating the immune response.

ROXANNE KHAMSI: Interesting, OK. So if I understand right, viruses like HIV and herpes, they actually get into the nucleus of our cells, that innermost part, and kind of get into the DNA and integrate there, but that there’s evidence that other viruses that don’t do that might be hanging around for a while because you say– as you say, they’re making proteins for a longer time?

DIANE GRIFFIN: Right. The ones like HIV and herpes– all the herpes viruses, actually– have mechanisms as a part of their natural replication for being able to, as you say, hang around for a lifetime, usually.

ROXANNE KHAMSI: So has our view on viruses changed? Is it still so clear cut that a virus sticks around or is cleared?

DIANE GRIFFIN: Yeah. So I think our views are changing because we didn’t really appreciate that this was an issue, whether it’s a problem or not, but whether it was an issue with these more acute infections. So influenza, you think of a lot of different– and, as I say, measles– a lot of different infections, where you’re only sick for a very short period of time. But now that we have these other kinds of techniques, we can appreciate the fact that, actually, the RNA or the genomes of these viruses also hang around for very long periods of time.

ROXANNE KHAMSI: Well, this is now making me think again about measles, what you’ve studied throughout your career. We thought for decades that we cleared measles. Measles happened, but then it was over, and that’s not the case. So there’s this study in Japan in the ’90s, where they looked at people who had measles as kids. What did that study tell us about measles?

DIANE GRIFFIN: Well, it was very interesting because they found– using these same kinds of techniques, they found RNA present at– in people who were dying, and they were quite elderly. Still present in a certain percentage. It wasn’t that they found it in everybody, but it indicated that it’s possible that some of these viruses can really stay around for a lifetime, although they don’t usually cause disease during that period of time.

ROXANNE KHAMSI: I mean, it’s not somebody you really want to hang around with for a lifetime, a virus. It’s a little scary to hear about this hanging around with us. But I know that you have studied measles very intensely. And I was wondering, what do we know about the mechanism for measles? Why does it hide out in the body?

DIANE GRIFFIN: Well, that’s a good question. And for measles, it’s hanging out in cells that actually turn over. So these aren’t really long lived cells, necessarily, but in– it’s primarily in lymphoid tissue, the tissue where the immune response is generated. So another thing that we know about measles is that it does establish lifelong immunity.

And not all viruses do that, but the fact that it remains and continues to stimulate the immune response over a long period of time may be one of the reasons or one of the mechanisms that it uses in order to be able to establish lifelong immunity, in which case that’s an advantage for the host.

ROXANNE KHAMSI: Yeah, it sounds like there’s an upside to having a virus for a while. It’s kind of stimulating the immune system and keeping us on alert, but not getting too dangerous. I mean, is there a risk of it going awry?

DIANE GRIFFIN: Well, that’s a good question, but it’s almost an epidemiologic question. But there’s not a way to know whether people are infectious or not, and that’s certainly been one of the major questions with SARS-CoV-2 is whether people, where you could detect the RNA by this RT-PCR kinds of mechanisms, are infectious are not.

For measles, it’s pretty clear. There’s not any evidence that the virus could be transmitted after maybe three or four days. After the rash has cleared, people are no longer infectious.

ROXANNE KHAMSI: So why aren’t you infectious if you’ve got measles in your body? That, to me, is a bit of a puzzle. If it’s hanging around for a while potentially, why wouldn’t you infect other people?

DIANE GRIFFIN: Right, but there seems to be a mechanism, and this is not something that we understand very well, for actually suppressing or clearing what we call infectious virus. And that’s whole virus particles that you could actually isolate in the laboratory and that would be what would be transmitted from one person to another.

The cells that were originally infected and producing the infectious virus for measles is in the– and for SARS-CoV-2 is in the respiratory tract, so viruses being produced in respiratory secretions. And that is what can spread it from one place to another. That virus is no longer being produced in respiratory secretions. Instead, inside the cells that were previously producing this kind of infectious virus, now they’re no longer producing the infectious virus, but they still have the genome inside the cells.

ROXANNE KHAMSI: One thing that is really important is that for those of us that got vaccinated against measles, we’re not going to have to worry about this thing of measles hanging around in us, right? Like if you’re vaccinated, you’re not going to have persistent measles in your body. Is that right?

DIANE GRIFFIN: I think that’s right. All of the evidence is that it is not doing the same kind of thing as the original, natural wild-type measles does. So it’s an attenuated virus that doesn’t replicate nearly as well as the wild-type virus.

ROXANNE KHAMSI: So with everything that you’ve uncovered with measles, how are we going to figure out if COVID persists in the body?

DIANE GRIFFIN: Well, I think that, first of all, as I say, some of the– first of all, we’re detecting the RNA for quite long periods of time, but it is variable from individual to individual. I think that it will become apparent whether people are infectious or not, as I say, mainly from the epidemiology of when they go home, do they infect people in their families, et cetera?

So these viruses are hard to culture. So I talk about infectious virus, and that means that you can culture it. And not only is it transmissible, but you can culture it in the laboratory. But that’s not an easy test. And people are– for the most part, are not culturing SARS-CoV-2.

ROXANNE KHAMSI: So viruses can hang around in the body much easier than sometimes they can hang around in a lab dish is what you’re saying?

DIANE GRIFFIN: Well, they can– or that you can recover them in the lab, yes.

ROXANNE KHAMSI: And I should say, we’re not talking about COVID persisting in the body, but SARS-CoV-2, the virus, just to be technical about it.

DIANE GRIFFIN: Right, right. Yes.

ROXANNE KHAMSI: So could this idea of persistence be playing into long-haul COVID?

DIANE GRIFFIN: Oh, I think so, yeah. And I think that’s probably one of the main hypotheses that is being pursued is whether there is persistence and where that is. One of the things that we know from measles is that that persistent RNA is continuing to stimulate the immune system.

So a lot of the symptoms of long COVID could be the actual immune response that is being generated, but it may be being stimulated by the virus hanging around or the viral genome hanging around and continuing to code for viral proteins so that they continue to be made even if you’re not making the whole infectious virus anymore.

ROXANNE KHAMSI: And I think that there’s debate around latency with COVID, whether or not it hangs around in our body and integrates into our DNA. But, I mean, in your opinion, do you think we should be looking for latency in COVID?

DIANE GRIFFIN: Well, I don’t think it’s going to– that there’s a big risk that it’s going to be integrating into DNA. I think that that’s one of the interesting things about these RNA viruses, and COVID is an RNA virus like measles is. They stay in the cytoplasm, so they don’t integrate into the DNA of the cells. Understanding how they’re persistent is a little more complicated than understanding it for HIV, for instance.

ROXANNE KHAMSI: Wow. I mean, it sounds like a big challenge. But speaking of challenges, you are on a committee that has put together a report on genetic surveillance in the US. What is the state of genetic surveillance?

DIANE GRIFFIN: Oh, I think it’s improved quite a bit. At the time that we put together our report, it wasn’t very good. It was much better in the UK, for instance, where they really had an organized system for monitoring these viruses and being then able to identify variants when they appeared in the population, but we’re now doing quite a bit better job. So we’re sequencing many, many more isolates or genomes that are circulating.

Mainly, SARS-CoV-2 is what’s being sequenced in monitoring these different viruses and knowing, for instance, right now that the Delta variant is an important strain that is actually being spread much more readily than some of the earlier versions of SARS-CoV-2. We also sequenced a lot of influenza viruses, where it’s very important to follow what the changes are over time.

ROXANNE KHAMSI: So that’s why it’s important to track viruses like this, right, to find out what they might be doing differently based on their genetic code?

DIANE GRIFFIN: Yes. We probably won’t find out about it from actually just the genetic code, but we’ll know to look for what the different– those each– those different viruses is doing and how it’s affecting in the population, as well as in the individuals who are being infected.

ROXANNE KHAMSI: I’m Roxanne Khamsi, and this is Science Friday from WNYC Studios. And taking the long view, you’ve been a virologist for decades. Why are viruses interesting to you? And is there some question about measles you’re still itching to crack?

DIANE GRIFFIN: We have– still have a lot of questions. And viruses are fascinating because they can do so many interesting things with– they have code for very few proteins, very few genes, but they take over a whole cell and organize the cell to be able to make them, the viruses. And so we learn a lot about cell biology, as well as about viruses and what they can do.

Right now, with measles, we’re very interested in how the– how you establish lifelong immunity, basically. So we think that the persistent RNA is a clue, but we don’t really know how it’s doing that. So we’re working hard right now to try to understand that and to understand the difference between wild-type measles and the vaccine strain of measles, how are they different.

ROXANNE KHAMSI: Well, I mean, I think these are great questions about viruses hanging around lifelong, and it seems like a question of lasting interest. We’ve run out of time, but I’d like to thank my guest, Diane Griffin, Professor of Molecular Microbiology and Immunology at Johns Hopkins in Baltimore, Maryland. Thanks, Diane.

DIANE GRIFFIN: You’re Welcome.

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