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Human endogenous retroviruses (HERVs) are ancient viruses found in our genomes, remnants of long-past infections. Elements of these viruses are activated by viral infections, and some play roles in devastating diseases like Multiple Sclerosis and ALS. Now it has been shown that SARS-CoV2 infection induces expression of specific HERV proteins. Prof. Claudia Matteucci discusses the role of HERVs and their tie to COVID19 diagnosis and potentially long COVID.
Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.
Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.
Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.
The Long COVID HERV Connection - Dr. Claudia Matteucci
Kevin Folta: [00:00:00] And today's guest is Dr. Claudia Machi. She's in the department of experimental medicine at the university of Rome. wow, you got me doing it. Here we go. Today's guest is Dr. Claudia Machi. She's in the department of experimental medicine at the university of Rome to regatta in Rome, Italy. Welcome to the podcast Dr.
Monte.
Claudia Matteucci: Hi, Kevin, thank you very much for this
invitation.
Kevin Folta: I am so happy you accepted this invitation because this has become my new favorite topic. Thinking about the way in which these endogenous retro viruses. Are exerting potentially a profound effect on different neurological issues, but maybe other health issues as well.
And so I really wanted to revisit this with you and and, and with our audience. And so we've had a few guests on the podcast discuss the role of human endogenous, retro viruses or hers in human disease, but can we recap for the listeners? What are herbs [00:01:00] and where do they come?
Claudia Matteucci: Okay. So the hurts are human INO Retrovir and endogenous means they are inside our cells, specifically our sequencing, our genome, they, our, our genome account for 8% of this sequence.
So they have a really important physiological rule in humans and they come from a surgeon of Retrovir. That have infected a million of years ago, PRI hates and then they are they infected the germ line and then by the time to pass to the offspring with evolution. And so they eed the genome of humans come from the evolution of this sequence through the time through all the species.
Kevin Folta: And, and this is really interesting to me. So this is something, I think you said 8% of the human genome, and this is a retrovirus that, that is a [00:02:00] Relic of ancient infections. That's been carried forward through primates. And so do I have that correct? Yes. Yes . And so what is the known associations between these endogenous retrovirus and human disease?
Claudia Matteucci: Okay. This hurts our part of the physiological rule. And so for example, for the developed ambience, but if there is a disregulation of depression alert this can be correlated to some symptom modification, expression of genes and protein that are associated to. Some disease, for example, cancer immunity neurological disease in this disease has been demonstrated at the regulation of
Kevin Folta: words.
Well, one of the interesting parts of this is we've had a number of guests on the podcast already speaking about the neurological manifestations in diseases like multiple sclerosis and ALS, but your [00:03:00] laboratory and your group of collaborators has seen an association of activation of specific aspects of, of these endogenous retroviruses coincidence with a SARS co V two infection.
So what is that Associa?
Claudia Matteucci: Yeah, this is right. We have found in the 2021, the first evidence that one pro coded from FW is over expressed at. In COVID 19 patient in particular, in the patient that have more severe condition and also in correlation with different clinical feature of the disease.
So the first evidence came from that first pub publication on this topic that came from our our lead.
Kevin Folta: And does it seem that there are different types of patients that express this Herve w at say different levels or show different clinical manifestations of the of COVID [00:04:00] that correspond very tightly with the Herve w presentation.
Claudia Matteucci: Yes. What we found is that the, for example, the patient that expressed more protein in the blood was the one, for example, that have higher expression of calculation marker of information. So there was a type of relation between expression and the clinical aspect.
Kevin Folta: And which types of cells express Herve w in response to the SARS co V two infection.
And why is that particularly important? So
Claudia Matteucci: the first evidence was on, on lymphocy and this was really interesting because you, we know that in COVID 19 one minute spec is the respo, the immune response this regulation, for example one minute spec is the, is tion of some lymphocy like CD eight.
That modify the functional activity during SAR [00:05:00] two infection. And what we found that the expression of the protein in lymphocy was directly correct correlate with the dysfunction of the immune response
Kevin Folta: may mention this is a dysfunction of the immune response, but are there any other. Maybe obvious ways in which this is associated with any of the symptoms specifically that we see presented during.
SARS co two infection. Oh
Claudia Matteucci: yes, we, for example, there was we found a correlation with problems in the respiratory dysfunction, the need for example of oxygen. So we correlated this also to specific symptoms of the disease. Of course we get, we went in the detail with the More like our cellular aspect.
There are correlated wheat,
Kevin Folta: and this is just a virus. I mean, SARS coy two is one of many [00:06:00] viruses that we're exposed to or that we, that we have to wrestle with that influenza a is another virus that's very different from the coronavirus, but it still causes somewhat related. Symptom spectrum similar pathologies.
And so is the Herve w protein that's being induced by the SARS co V two virus in specific lymphocytes. Do we see that also with other viral types?
Claudia Matteucci: Oh, yes. We can say that. Is this known that the exposure to stimuli different stimuli of the cell by any kind of stim? These also microbes infection could modify the ion of earth.
And for example, for HIV, for embar, for other Apress virus has been already demo say that different heart can been activated and also FW, for example, for Apress virus, virus, and The response to the infection induced [00:07:00] protein, but it's also to the DYS that can relate also to other kind of disease that are not, are not directly linked to infection.
Kevin Folta: And you mentioned the genes that are expressed, and this has been something your group and the publications have shown it shows that there are increased expression of genes that are associated with inflammatory response. So is this the the body's response against specific types of viruses and maybe kind of a protective role?
Or do you imagine this might be something that is just a co. A problem that comes along with the infection.
Claudia Matteucci: Okay. There is it is known that FW protein can interact for, with total receptor four. So this specifically, this protein can induce. The inflammatory response, the proinflammatory response, and we know that Cy cytokine storm, so call it cyto storm.
So the induction of different proinflammatory [00:08:00] cytokines is a massive in COVID patient. And this is a, a particular issue of the disease. Indeed, several therapy at the beginning. Just to stop in some way to naturalize, this Proin inflammatory side against, but her w specifically can induce it. So it's not only that these things goes together, but her w is a cofactor of this
Kevin Folta: aspect.
Okay. So her w really seems to be the. Causal agent in, in this inflammatory response of cytokine storm. So is there a important predictive value in understanding Herve level or Herve RNA levels or protein levels that can help you make better decisions about the di diagnostics or treatment of a given patient?
Claudia Matteucci: Okay. First of all, I would like underline that HW is a cofactor of the disease. Let's say [00:09:00] that satin storm. Could be probably induced also to, from other aspect during the, and the Sarov two itself, indu the, the, the sat storm. So I would like to speak of her w as a cofactor and we are studying expression of art and also the, of other arts as a Marcus predictive of the response.
So we are we have a project that have the him to use heart as diagnostic tool adults, also predictive marker. For example, of the disease, maybe in the future, also of target for.
Kevin Folta: Oh, very good. This is a really great start to introduce what these herbs are, what her V w is it's association with SARS co V two infection.
And when we get back from the break, we'll talk more about its role in other diseases. So we're speaking with Dr. Claudia Mai [00:10:00] she's in the department of experimental medicine at the university of Rome. Tover Gaza in Rome, Italy. This is collaborates talking biotech podcast, and we'll be back in just a.
And now we're back on the talking biotech podcast by collab. And we're speaking with Dr. Claudia Machi. She's in the department of experimental medicine at the university of Rome to regatta. And we're talking about herbs, specifically, herb w as a protein that's being expressed from ancient retroviral sequences that are resident in our genome that are woken.
By a SARS co to infection and potentially has a role in the long term effects that we're seeing from COVID 19 infection and issues, especially that it may be neurological. And we'll explore that in the second part of the podcast. So I'm curious about the role of Herve w in other diseases let's start there.
So what do we know about [00:11:00] Herve w and the pathology that's created in say Ms or ALS or other disease?
Claudia Matteucci: Yeah. It's already known that her w is hover expression in patient with multiple sclerosis with diabetes in psychiatric, also patients. And it is already known that. In this disease, that her w is very expressive, for example, in Ms in microglia.
And that can directly be a cofactor of the disease. And indeed there is a lot of research about this already published and also there is also the possibility to do trials on Ms and diabetes patient targeting our w.
Kevin Folta: It it's really interesting to me because it wouldn't occur to me as a researcher to even look for it.
But, but of course I don't work in this particular area, but let's talk about the other herbs. Has anyone looked for or detected Herve [00:12:00] K or Herve, F R D any of the other Herve associated proteins or transcripts in response to SARS co V two? I.
Claudia Matteucci: Yes, it is. There, her key expression is already has been already found in, for example, in NACU there are people that publish this data and we are also we have data on this.
And also Ahart for example, in LAR fluid has been found. And as I told you, the infection can reactivate or modulate expression of different earth because the heart in our genome are a lot different sequence, different family, let's say group of families. And so what we the aim of one of our the main project we are following that is an European project on COVID.
And we will study different types, not only FW.
Kevin Folta: And maybe this is just me [00:13:00] speculating, but we hear a lot about long COVID and these presentation of neurological symptoms. So whether it's what they would refer to loosely as brain fog, you know, this inability to process quickly maybe other manifestations of fatigue, other issues is there any.
Really strong evidence of a connection between Herve w expression and patients with long COVID.
Claudia Matteucci: Yes. To date the long term health problems, including neurological symptoms, such aheadache fatigues. Memory loss of confusion are really problem for the post COVID patient and is particular presenting those patients that are called long.
They, they have a long COVID and we are also focusing in post COVID and lung COVID with this, with our project. And we have found that still expression of the protein in the blood in lung patient. Is [00:14:00] correlated with some of these symptoms, for example, with Persia or pre it is suggests that there is an involvement of Sarco two or sorry, of R w and other her in the neurological direct that are related to COVID 19.
Kevin Folta: And, and all of this is really a very rapidly emerging field. So I totally understand, you know, we're speaking of with a fair degree of speculation, but the observations that these neurological symptoms seem to correlate very strongly with the blood levels of Herve w. We know that there are neurological diseases that can be treated at least in clinical trials with this new monoclonal antibody approach that is directed at Herve w and they've been tested for safety.
They look good in clinical trials. Are these potentially useful tools for mitigating the effect of, of COVID 19 and maybe long COVID.
Claudia Matteucci: Yes, as you tell, there is a [00:15:00] mono antibody that's called from Genero. And this is, has been already used to treat Ms and diabetes. And we are start, are going to start in our hospital in the future, a trial.
On post COVID with this antibody. And and also in Europe, other center will start to do it. So there is the object to try to stop block and naturalize this problem in post COVID. And to verify if we can diminish the symptoms of this aspect of the.
Kevin Folta: It really sounds important. It seems to me that this may become a, a, a first point of care in someone who presents with SARS co V two infection because of the potential neurological disorders and the apparent safety of the monoclonal antibody.
So this seems to be a really good step forward, but along that. [00:16:00] It seems like different patients have different levels of Herve w but also different levels of symptoms. And so how does that variation between patients really shape those point of care decisions to deliver the most appropriate treatment?
Claudia Matteucci: Yes, we in our study, since we are studying her w but also there, her, we are trying to verify if the different expression profile of desserts. Together with the all other aspect, like the inflammatory aspect are tools as predictor markets. And we know already that we can predict at the date of hospitalization, which will be the outcome of the patient.
Because we demonstrate that at the first time of detection of w at the emergency, then we know that other three weeks, the ones that have higher special of w [00:17:00] are the ones that needed the oxygen support.
Kevin Folta: And are all Herve Ws the same. I, we say that there's 8% of the genome is human endogenous, retro viruses.
But do we see sequence polymorphism between the different part, different ones that come from the genome? Do we see heterogeneity and is there any evidence that specific variants that maybe one patient may carry over another may contribute disproportionately to the symptoms that we see?
Claudia Matteucci: Yes, actually, you, we know that we see that the response to this infection globally is really it OUS.
And we have a lot of people that get infected and they are as symptomatics and those that goes in hospitalization, they have really those that are unfortunately die for disinfection. So uh, one point is for our project is to put her has this markets and [00:18:00] cofactor because they are different sequence in different individual.
We have polymorphism among all the population and we know that we can use this hurts. Also to try to understand why there is a different response to CSO infection.
Kevin Folta: Well, based on all of this. So we're talking about this very strong correlation between the activation of Herve w this presence of this protein and people with more severe symptoms, does it really underscore the urgency to avoid infection?
Make sure you're vaccinated and take every precaution you can take to not get a SARS co two infection.
Claudia Matteucci: Okay. It's it's difficult to think that we can avoid infection if you see how much is spreading the virus. And but all duplication of course are important. We have to try to. Use the all [00:19:00] the tools to try to prevent defection at the same time, the vaccination is really important because with vaccination, we know that you can get infected, but then you don't have the more symptoms you don't have, the, you can avoid the severe disease.
So a vaccination is really very important.
Kevin Folta: Yeah, it seems like this is a emerging area that is extremely exciting. And just to, just to not not get the infection, seems like a good move or do as best you can to avoid it, I guess. So we see this kind of difference in response to the SARS co V infection between different patients.
We see that it correlates with Herve w levels and does. Difference between different patients really shaped the delivery of the most appropriate treatment to individual patients.
Claudia Matteucci: Yes, we, we as a focus of the European [00:20:00] project at co, we want to use Hertz as tools for a personality treatment of COVID patients.
So due to day, ity of the response to disinfection at the same time, the Turgen of the sequence present in our genome. Related to Hertz. We opened that our study, our project European study that is start three months ago and it will last five years will bring information to use Hertz as target for therapy, but also market to predict the response to, for each individual patient.
Kevin Folta: No very good, because as we can shape individual patient treatments, you can kind of customize them with the appropriate therapies. And it won't be a question of just throwing everything at a given patient, being able to shape the treatment based upon the presentation of the disease based [00:21:00] upon these good biomarkers which is really exciting.
So if people wanna learn more about the project or more about your laboratory, where would they.
Claudia Matteucci: Yes, they can look on scientific publication looking for hearts and COVID 19, and he will found some article and they are rising every. Mouth we are strive to, to found more. And and then you can find information of our European project on Cordy website for, from UA.
And also we have a website for our project and the Twitter. So please let read and also speak and discuss.
Kevin Folta: Yes. And the Twitter handle for that. The username is at her Cove project, H E R V C O V P R O J E C T. So that's where you can learn more on Twitter. And I definitely will [00:22:00] follow that one because I think this is an exciting story and an emerging story, and I hope that as you learn more, could you please let me know and let's continue this conversation.
Thank you very much for joining me.
Claudia Matteucci: Thank you very much, Kevin. It was a pleasure and a really high hope this kind of talk and this is really help scientists, but I think this could be accessible also to common people that as is not an expert in
Kevin Folta: this. And for everybody listening, thank you for listening to another week of the talking biotech podcast.
This is a story to watch that as we begin to see this dovetailing of SARS co two infections, it's the other side of COVID could have a role in the long term issues that we're seeing arising in some individuals and could have important ramifications for your health and your family's health. Your community's.
So stay tuned. This is the talking biotech podcast and we'll talk to you again next week.[00:23:00]