Cytomegalovirus can harm those with weakened immune systems

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center.

I'm your host, Amber Smith.

Today, we'll learn from one of Upstate's scientists about the human cytomegalovirus. Dr. Gary Chan recently received a substantial federal grant for his work on this virus.

Dr. Chan is an associate professor of microbiology and immunology at Upstate.

Welcome to "The Informed Patient," Dr. Chan.

Gary Chan, PhD: Hi, Amber. How are you?

Host Amber Smith: I'm great, thanks. I'd like to start by having you tell us about human cytomegalovirus. Is it true that up to 80% of the population carries this virus?

Gary Chan, PhD: Yeah. What you can say is it's called a dormant virus or silent virus. Once we're infected, we have it for life, and about 80% of us have it, just depending on different populations and where you live, but on average in the world, about 80% have it.

Host Amber Smith: Is it important to know whether you have it or not, or if it's dormant, does it not cause any trouble?

Gary Chan, PhD: For the most part, it doesn't cause much trouble, but it is important for you to know. It's important for when, if you ever need blood transfusions, transplants and things like that, at that point, the virus, you could say, quote unquote, "wakes up," it can cause a lot of problems.

Host Amber Smith: So how are people infected, or how does the virus spread from person to person?

Gary Chan, PhD: It's really through infected fluids, bodily fluids. The major point of transmission is usually when you're adolescent. So when you're a little kid, you get infected, a lot of the times, (it's) mothers kissing their kids, kids sharing food and all that. That's when most of it is spread.

Host Amber Smith: What does the virus do? I know you said it's dormant, mostly, in the body, but does it do anything while it's in there?

Gary Chan, PhD: Yes and no. For the most part, it stays pretty quiet, but every once in a while, if you're stressed, like any other herpesvirus -- many of you have heard of chickenpox before -- there are stresses that can wake this virus up.

And usually our immune system is pretty good at just stopping this virus from spreading too far.

Host Amber Smith: Do you know, is it one of the viruses that are tested in donor blood, like for the nation's blood supply? Do they test and look for this before they pass it to someone else?

Gary Chan, PhD: Yeah, absolutely. They screen for this virus now, and they have to know, especially for blood transfusions during transplants and things like that, they have to know whether you're CMV positive. In people who don't have strong immune systems, this virus can cause a lot of disease, which is why the NIH (National Institutes of Health) is very interested in this virus.

Host Amber Smith: And you got your grant from the National Institutes of Health, which I'm going to ask you about. But I'm still curious: CMV, cytomegalovirus, does it produce any symptoms? Would a person know that they have it by symptoms?

Gary Chan, PhD: In general, when you first get infected, it doesn't cause much problems.

It can sometimes lead to mononucleosis, or "mono." There's a couple viruses that cause that. CMV is one of the viruses that can cause that, so if you're healthy, that's probably the most extreme you can get. But, that said, with healthy individuals who have a full immune system, it has been associated with a lot of different cancers, and there are a lot of herpesviruses that actually can cause cancers.

And CMV -- I'm not going to say right now it's known whether it causes cancers, but it is definitely associated with a lot of different cancers, and it's an active field of research right now.

Host Amber Smith: How long has science known of this virus's existence?

Gary Chan, PhD: Probably since around the '50s. There's three scientists independently, I think it was Margaret Smith and Thomas Weller and W.P. Rowe. They all independently discovered this virus, got together, and we've known probably for about 70 years of the virus. We haven't really been able to study it much, since until really the '80s, when we actually had the tools to be able to study a virus.

Host Amber Smith: Is the potential connection to cancers a newer development?

Gary Chan, PhD: Yeah. There's other herpesviruses that they know do cause cancers. EBV, or Epstein-Barr virus, is one of those herpesviruses. CMV has a lot of the similar traits, and so they always thought that it could cause or lead to viruses. And so there's a lot of people who are actively studying it right now, and they do find a link.

One of the big ones that everyone is studying right now is with glioblastomas. It's been associated with a lot of glioblastomas and breast cancers.

Host Amber Smith: Can CMV be treated?

Gary Chan, PhD: Yeah, there's a few antivirals that are out there. I won't get into the weeds, but it targets a protein, this antivirus target protein that's expressed (produced) by the virus that needs to replicate.

And most of these antivirals will stop the replication of this virus, so it'll never get rid of the virus because the virus lies dormant inside of us. But once it activates during a person who is immunocompromised, you can give these antivirals to prevent the virus from replicating.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with Dr. Gary Chan. He's an associate professor of microbiology and immunology at Upstate, where his lab focuses on studying the human cytomegalovirus.

The National Institutes of Allergies and Infectious Diseases recently awarded you more than $3 million to put towards your research.

Can you tell us about the work your lab is doing?

Gary Chan, PhD: The CMV causes a broad array of diseases. Lots of different organs can get affected, and so what my lab is really interested in is studying how this virus is able to spread around the body and how the virus hides from the immune system by laying dormant.

And so half of my lab studies basic biology, trying to understand how this virus is able to spread around the body, how it's able to cause disease and what unique changes that it causes to cells into the body so that we can target it.

The other half of my lab then takes the information that we learn from one half of the lab, the basic biology, and then we try to develop antivirals to target some of those unique changes that the virus makes to the cells, so we're able to target and maybe eliminate some of the infected cells within the body and prevent spread and prevent disease.

Host Amber Smith: At this point, and I know it's early, but do you know, does this virus behave like another virus?

Gary Chan, PhD: There's a whole bunch of herpesviruses out there, right? And it behaves similar to them. It has a lytic -- active -- infection, where it's replicating. It has a silent stage. All herpesviruses do that, so it's very similar in that way. In terms of how it spreads around the body, it can be a little different. It uses a specific cell type, they're called monocytes, they're a type of white blood cell, and it uses them to basically piggyback off of monocytes to spread around the body. Some of the other herpesviruses target different types of cells, but the basic principle of it being awake and asleep is similar among all the herpesviruses.

Host Amber Smith: Are you planning, or do you hope to come up with, a more effective treatment for CMV through some of this research?

Gary Chan, PhD: Yeah, that's the ultimate goal. Right now some of the problems with the current antivirals is they have a lot of severe side effects, and they target really a protein that's expressed by the virus. And because of that, it can develop resistance to these antivirals.

So my lab is taking a slightly different approach. We're trying to target cellular proteins, so proteins within the cell that the virus uses to replicate. And by targeting the cellular proteins, it's unlikely that these cellular proteins are able to mutate. And so if you target cellular protein, you can prevent replication.

It's unlikely that you'll develop resistant strains.

And on top of that, what we try to do is try to identify proteins that are really only activated within an infected cell, to limit the side effects.

A lot of types of treatments, if you target just a general protein, it can lead to lots of side effects if it's needed for just normal function. So we're trying to identify proteins that are only within a stressed cell, like a virally infected cell.

Host Amber Smith: And so these treatments really would be aimed to help someone who's immune compromised.

The general public doesn't necessarily need treatment day-to-day for this.

Gary Chan, PhD: Yeah, correct.

Host Amber Smith: But if someone suddenly, developed kidney disease and was in need of a transplant ...

Gary Chan, PhD: Uh-huh ...

Host Amber Smith: ... they would perhaps find themselves with a compromised immune system, and this will be very important, it sounds like.

Gary Chan, PhD: All transplants, you're screened for CMV, and if the donor or the recipient is CMV positive, you're automatically put on preemptive or prophylactic antivirals to prevent replication of virus. So this will work in a very similar way. We can predict high-risk patients, and in those high-risk patients, we can give these antivirals early so that when the transplant happens, it prevents replication of the virus right from the beginning.

Host Amber Smith: Are you and the rest of the scientists in your lab concerned or worried about catching CMV through your work?

Gary Chan, PhD: There's always a little bit of risk involved, but the viruses we generally work with are lab-adapted, so they've been out of a human body for so long that it's unlikely that we can probably get infected by these strains of viruses.

They've changed probably enough, once we've pulled them out of the body and isolated them. And you grow them in tissue culture. They lose a lot of these proteins that are needed to infect a human being. So for the most part, we're safe unless we take clinical samples. In that scenario, then there is a risk, but we are pretty safe. We've tested all of us, and everyone in our lab is CMV positive, so we already have immunity against it.

Host Amber Smith: Can you talk about how humans can coexist in a world with potentially dangerous viruses like CMV, cytomegalovirus, and also, SARS-CoV-2 (COVID), which we're dealing with globally for three years and ongoing? How do we coexist?

Gary Chan, PhD: It's interesting that they're two very different viruses. With CMV, you would argue that we are coexisting because 80% of us have it. It doesn't cause a lot of disease.

This virus was actually, honestly, was probably here before we were here. So the virus didn't learn to coexist with us, we evolved to coexist with this virus, because it was already here. And we've learned to live with this virus for a very long time, and it really doesn't cause much disease or a lot of disease, unless you're immunocompromised.

With SARS-CoV-2, it's very different. It has (been) learning to live with us, right? And so the virus came, right? We were here before it came, and it caused a lot of disease. Over time, the virus will cause less disease, and we'll eventually learn to live with that virus as well.

But in the end, I think, with a lot of these viruses, whether it's SARS-CoV-2 or whether it's CMV, which are really endemic at this point throughout the world, we're just going to have to learn to live with it and develop some antivirals and more take (an) approach of protecting the vulnerable people versus trying to eliminate the virus completely, which I'm not sure if that's possible at this point with either virus.

Host Amber Smith: I was going to ask that. Could you, even if you set out to, eliminate CMV? That wouldn't really be possible, it doesn't sound like.

Gary Chan, PhD: Yeah, it would be really difficult because it's in most of us already. Maybe if you had developed a vaccine, and you give it to all kids and over a long period of time, but that would be a massive undertaking.

And currently there is no vaccine for CMV. It's one of the largest human viruses out there. It's really complicated, and so to develop a vaccine would be the first step, but even then, most people, especially in this day and age, aren't going to just take a vaccine if they don't feel unwell.

So it's more protecting the people who are vulnerable is the approach we need to take right now.

Host Amber Smith: And so your lab is doing that. If you're able to come up with a more effective treatment, it doesn't eliminate the virus, but it controls it.

Gary Chan, PhD: Correct. Right. And in the vulnerable population, particularly in transplant patients or any type of immunocompromised individual.

Host Amber Smith: Well, thank you so much for making time for this interview, Dr. Chan.

Gary Chan, PhD: No problem. Thank you for having me.

Host Amber Smith: My guest has been Upstate microbiology and immunology associate professor Dr. Gary Chan. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

Find our archive of previous episodes at upstate.edu/informed.

This is your host, Amber Smith, thanking you for listening.