Speaker 1: Hi, I'm Aaron Welsh and this is this podcast will
Speaker 1: Kill You. Welcome to another bonus episode in this mini
Speaker 1: series of bonus content that we've been putting out over
Speaker 1: the past couple of months. If this is the first
Speaker 1: time you're tuning into one of these and wondering what
Speaker 1: this is about. I've been putting together these bonus episodes
Speaker 1: to explore in more detail one aspect of the topic
Speaker 1: that we covered in our previous week's regular season episode.
Speaker 1: I've also been using this opportunity to chat with people
Speaker 1: about their jobs, what they like about them and what
Speaker 1: they don't, how much they do changes from day to day,
Speaker 1: and any words of wisdom they may have for people
Speaker 1: just starting out in their careers. So far, I've gotten
Speaker 1: to chat with some fantastic folks about hepatitis B, stigma
Speaker 1: and discrimination, a new drug for human African tripanisimiasis rabbit
Speaker 1: hemorrhagic disease virus, and it's been fascinating to see how
Speaker 1: wide ranging this work can be and how many different
Speaker 1: approaches can be used in the field of public health.
Speaker 1: This week, I'm taking a bit of a zag from
Speaker 1: last week's episode on multiple sclerosis by turning my sites
Speaker 1: to the epstein bar virus, helped along by doctor Mika Luftig,
Speaker 1: Associate Professor, Vice Chair in the Department of Molecular Genetics
Speaker 1: and Microbiology at Duke University. Last week, Aaron and I
Speaker 1: covered multiple sclerosis, which is a disease of many mysteries.
Speaker 1: Go and check out the episode if you haven't already
Speaker 1: one of these mysteries, which could be considered the central
Speaker 1: mystery really is what causes this disease. Recently, a couple
Speaker 1: of studies were released that shed a bit of light
Speaker 1: on this aspect of multiple sclerosis, especially as it relates
Speaker 1: to the epstein bar virus, a virus that has long
Speaker 1: been suspected to play a role in this and many
Speaker 1: other diseases. In the case of MS, there doesn't seem
Speaker 1: to be one single cause for what makes some people
Speaker 1: develop this disease, and it's likely many factors working together,
Speaker 1: such as a lack of vitamin D, genetic predisposition, a
Speaker 1: history of exposure to cigarette smoke, and epstein bar virus.
Speaker 1: But it does seem as though EBV is probably a
Speaker 1: crucial part in the development of this disease. In our
Speaker 1: MS episode, we talked about the implications of this recent
Speaker 1: research about EBV and MS and what it could mean
Speaker 1: for the prevention or treatment of multiple sclerosis, and that
Speaker 1: discussion it also got me thinking just more about this
Speaker 1: bizarre virus, that epstein bar virus, and what about its
Speaker 1: biology has led to it being implicated in all kinds
Speaker 1: of cancers and autoimmune diseases beyond multiple sclerosis. So I
Speaker 1: wanted to use this bonus episode to get up close
Speaker 1: and personal with this extraordinarily prevalent virus this bonus episode.
Speaker 1: It doesn't mean that EBV won't someday get the full
Speaker 1: erin squared treatment in a regular season episode, but who
Speaker 1: doesn't love a little sneak peek. Since its discovery in
Speaker 1: nineteen sixty four, the epstein bar virus has been implicated
Speaker 1: in an impressive number of different diseases, including various cancers
Speaker 1: and autoimmune diseases, just as we found in multiple sclerosis episode.
Speaker 1: There are still many mysteries and unanswered questions that surround
Speaker 1: the epstein bar virus, but over the years we have
Speaker 1: also made incredible strides in understanding how it does the
Speaker 1: things it does. One of the researchers who has helped
Speaker 1: to answer those formerly unanswerable questions is doctor Mika Luftig.
Speaker 1: Doctor Luftig has graciously agreed to submit to my many questions,
Speaker 1: not just about the epstein bar virus, but also what
Speaker 1: it's like to be a professor, what other options are
Speaker 1: out there for someone interested in viruses and microbiology, favorite
Speaker 1: virus fun facts, and so much more. I'm going to
Speaker 1: take a quick break here and then I'll let him
Speaker 1: introduce himself.
Speaker 2: I'm Nikoleptik. I'm an associate professor and the vice chair
Speaker 2: here in the Molecular Genetics and Microbology Department at Duke
Speaker 2: University School of Medicine. My lab studies EBV epstein bar virus. Primarily,
Speaker 2: we've studied how EBB infects and immortalizes human B cells
Speaker 2: and that's a model for lymphomas in immune suppressed patients.
Speaker 1: Thank you so much for joining me today. I am
Speaker 1: so thrilled to get into the nitty gritty of epstein
Speaker 1: bar virus. So what is EBV? Can you tell me
Speaker 1: a little bit more about this virus, what type of
Speaker 1: virus it is, how do people get it, and what
Speaker 1: makes this virus so special.
Speaker 2: EBV is a herpes virus, so it's in the family
Speaker 2: of We currently know there are eight human herpes viruses,
Speaker 2: and EBV is, like all herpes viruses, a large, double
Speaker 2: stranded DNA virus, and what that means is that its
Speaker 2: genome is made up of the same material as human genomes,
Speaker 2: and so that material is packaged up into a protein
Speaker 2: shell and decorated on the surface with glycoproteins, which we've
Speaker 2: heard a lot about in the news in the last
Speaker 2: two years. And this virus is complex because of its size,
Speaker 2: so it's about one hundred and seventy thousand bases long,
Speaker 2: and it can encode about eighty different proteins as well
Speaker 2: as a bunch of little RNA gene products that help
Speaker 2: take over the cell. It's special because it has an
Speaker 2: intimate relationship with humans. Virtually every adult on the planet
Speaker 2: is infected with EBB, and you're infected when you're a child,
Speaker 2: usually in the first decade of life. The virus is
Speaker 2: transmitted by saliva, so it could be your mom or
Speaker 2: dad kissing you, it could be from another kind of
Speaker 2: kiss that happens in young age, and usually the infection
Speaker 2: is relatively benign. But what happens is that the virus
Speaker 2: gets into the cells called B cells, which are the
Speaker 2: antibody producing cells in your immune system, somewhere in your
Speaker 2: oral mucosa, like your consoles or adenoids. And when that happens,
Speaker 2: the virus goes latent, and that's really the where the
Speaker 2: intimacy starts. The latently infected cell can harbor the virus
Speaker 2: more or less for your whole life.
Speaker 1: Can you talk a little more about what's going on
Speaker 1: at the cellular level with EBV infection?
Speaker 2: You know, I keep bringing up B cells, which maybe
Speaker 2: most people don't think about as much as I do,
Speaker 2: but it's sort of an important cell type to think
Speaker 2: about because the virus has evolved clearly to take advantage
Speaker 2: of being latent and living in a B cell and
Speaker 2: mimicking how B cells normally respond to antigens. So, because
Speaker 2: they're antibody producing cells of the human immune system, their
Speaker 2: goal is to have an antibody on the surface of
Speaker 2: the cell that sees an antigen from some pathogen get excited.
Speaker 2: The cell starts to divide and make better and better
Speaker 2: antibodies that ultimately are used to fight whatever that pathogen was. Well.
Speaker 2: EBV sort of takes advantage of that process and has
Speaker 2: specific proteins that mimic the kinds of proteins that get
Speaker 2: activated in cells when they see antigen and drives that
Speaker 2: same process that B cell would have done if it
Speaker 2: had seen some foreign pathogen. And so the end goal,
Speaker 2: I'm like cutting to the chase here of why this
Speaker 2: thing is so successful and so amazing, is that the
Speaker 2: end goal is that the infected B cell that starts
Speaker 2: off in your tonsils or rev you ends up as
Speaker 2: a memory B cell in your blood, which just sits
Speaker 2: there for weeks or months or longer. When the virus
Speaker 2: is completely late, we can get into the nitty gritty
Speaker 2: of what the latent replication cycle is like, because it's
Speaker 2: not the typical replication cycle you think of a virus
Speaker 2: where you make new particles and you get out. It's
Speaker 2: actually just the viral genome is circularized as an extra
Speaker 2: chromosomal piece of DNA. Then you start with one, you
Speaker 2: wind up with about ten in the memory B cell compartment.
Speaker 2: But when say anagen comes and triggers that B cell
Speaker 2: to think that it needs to make a ton of antibody,
Speaker 2: that's a dead end for the virus and it switches
Speaker 2: to the lytus cycle, which for EBV the way it
Speaker 2: happens is that these latent infected B cells, anagen comes
Speaker 2: reactivates it. Now you make thousands of particles that are
Speaker 2: released from the cell. That starts a life cycle of
Speaker 2: then the other phase, which is in epithelial cells, so
Speaker 2: cells in the oral mucosa. When the virus gets out,
Speaker 2: it will go in and instead of doing that whole
Speaker 2: latency dance that I just described, that sort of beautiful
Speaker 2: B cell latency dance, it just replicates like any other virus,
Speaker 2: you know, the textbook example of it gets in, it replicates,
Speaker 2: produces tens of thousands of particles, kills the cell. And
Speaker 2: that amplification step is actually what's happening in all of
Speaker 2: us and why the virus is released into the saliva
Speaker 2: and getting out to be able to transmit to others,
Speaker 2: but also to infect new B cells in your oral nucosa.
Speaker 1: Okay, I see. And so in that initial infection it
Speaker 1: goes into the B cells and then eventually it will
Speaker 1: go into the epithelial cells when it is actively shedding virus, right, gotcha? Okay?
Speaker 1: And so many or even most people who get EBV
Speaker 1: may not ever know it because it doesn't produce any symptoms,
Speaker 1: But what about when it does, Like, what are the
Speaker 1: symptoms of a symptomatic EBV infection and what's going on
Speaker 1: at a cellular level that can lead to those symptoms.
Speaker 2: I'll even step back and answer the question of why
Speaker 2: don't people get sick when they're infected with EBB Because
Speaker 2: it turns out that EBV latency proteins are exquisitely well
Speaker 2: recognized by the T cell response of the human immune system,
Speaker 2: and so in adults, one to two percent of all
Speaker 2: of your T cells are specific for EBV proteins. They
Speaker 2: are activated and will eliminate those latently infected cells that
Speaker 2: are producing the viral proteins pretty efficiently for your whole life.
Speaker 2: And so it's only either in the case of immune suppression,
Speaker 2: where EBV can cause problems in the B cell compartment
Speaker 2: and where you become much more susceptible to the lymphomas
Speaker 2: that EBB can drive. We can talk more about that
Speaker 2: in a bit. But where it causes disease though, first,
Speaker 2: so to speak, in most folks life is in the
Speaker 2: second decade of life. So if you're not infected in
Speaker 2: the first decade of life, then it can be a
Speaker 2: problem because about fifty percent or so of those primary
Speaker 2: infections cause mono. So EBV causes infectious mononucleosis. And the
Speaker 2: reason that happens is that the same dance of the
Speaker 2: latent infection in the B cells happens, but the T
Speaker 2: cell response, in fact is over exuberant, and you will
Speaker 2: have on the order of half of all of your
Speaker 2: T cells in the blood will be EBV specific for
Speaker 2: a couple of weeks. And that massive systemic expansion of
Speaker 2: T cells and the cytokines that they produce is what
Speaker 2: causes the fatigue and symptoms of mono. And there is
Speaker 2: a failure of those T cells to get to the
Speaker 2: tonsils the world ecoso where the EBB infected B cells
Speaker 2: are to shut things down in essentially anyone older than
Speaker 2: an adolescent if it's your primary infection. And that's a
Speaker 2: great mystery, immunological mystery. But the idea of having a
Speaker 2: vaccine that in individuals that are not yet infected could
Speaker 2: potentially prepare your immune system to deal with that primary
Speaker 2: infection later in life could be something that prevents mono
Speaker 2: and that could have also further benefits down the road.
Speaker 2: So it's not the B cells that are infected that
Speaker 2: cause disease in mono. It's the massive expansion and failure
Speaker 2: of contraction really of the T cell response that is
Speaker 2: very interesting.
Speaker 1: So, besides the age differences in terms of when you're
Speaker 1: first exposed to eat, do we know anything more about
Speaker 1: what determines whether or not you'll have a response to
Speaker 1: EBV infection or primary EBV infection.
Speaker 2: From the standpoint of everybody is going to be exposed
Speaker 2: to this virus, right, so the vast majority of people
Speaker 2: follow the course that we just described. But because so
Speaker 2: many people are infected, turns out that there are genetic
Speaker 2: variants that families can have where the individual is not
Speaker 2: able to control that primary BV infection and B cells
Speaker 2: because they're T cells, are in some way unable to
Speaker 2: see and kill the infected B cells. And I say
Speaker 2: it that way because it turns out some of the
Speaker 2: biology and the immunology that's been done on these questions
Speaker 2: actually detect not necessarily wholesale T cell immut deficiencies, but
Speaker 2: specific defects where T cells can't recognize B cells, and
Speaker 2: if they can, if there's either a transplant, for example,
Speaker 2: of mautaquatic stem cells or T cells that can come
Speaker 2: in to preserve that function. Then they can eliminate the
Speaker 2: B cells, but the T cell response to other viruses
Speaker 2: may not be deficient. So there is now an emerging
Speaker 2: recognition and field around what we would call chronic active EBV,
Speaker 2: and that is an umbrella under which individuals that have,
Speaker 2: for example, excellent glympho proliferative disease XLP, which is caused
Speaker 2: by a couple of different mutations that can prevent the
Speaker 2: T cells from interacting with the B cells, and other
Speaker 2: genetic variants that prevent T cell activation and T cell
Speaker 2: killing of the EBV infected B cells. And so then
Speaker 2: there can also be spontaneous or somatic mutations like happen
Speaker 2: for example, in cancer progression, but in the immune system
Speaker 2: where those somatic variance end up causing an inability, you know,
Speaker 2: for T cells to recognize the EBV infected cells. And
Speaker 2: so in some that sort of umbrella of diseases that
Speaker 2: one could lump together as chronic active EBV are what
Speaker 2: would lead to folks basically not being able to control EBV,
Speaker 2: and the consequences of that can be pretty severe, but
Speaker 2: range from monol like symptoms recurring what can be as
Speaker 2: severe as developing lymphomas or other EBV associated cancers.
Speaker 1: EBV is involved with many different types of cancers. Can
Speaker 1: you talk a bit about how infection with EBV could
Speaker 1: lead to cancer development.
Speaker 2: By the numbers of patients, eb V associated gastric cancer
Speaker 2: is the most prevalent EBV positive cancer in the world.
Speaker 2: Almost two hundred thousand people ten percent of gastric cancers
Speaker 2: are EBB positive, And what that means is that not
Speaker 2: the person is EBB positive, the cancer is EBB positive.
Speaker 2: So every infected cell in the tumor has EBB in it.
Speaker 2: So how the heck could that happen? Turns out that
Speaker 2: EBV doesn't really like infecting epithelial cells on its own
Speaker 2: in the lab, Whereas if you take a latently infected
Speaker 2: B cell and you cocultureate with epithelial cells that are
Speaker 2: uninfected and you reactivate the B cell, that triggers reactivation
Speaker 2: and transfer of the virus through cell to cell contact
Speaker 2: to the epithelial cells a thousand times more efficient than
Speaker 2: if you did a direct infection. So piecing that all
Speaker 2: together and the fact that in gastric cancer you often
Speaker 2: have an underlying gastritis, sort of chronic infection dysbiosis in
Speaker 2: some way that is a precursor to the cancer. It
Speaker 2: is very likely that EBV infected b cells that have
Speaker 2: an antibody on their surface with a specificity for some
Speaker 2: of the bacteria that might be causing the gastritis home
Speaker 2: to the basal basolateral surface of the epithelial cells in
Speaker 2: lymphoid tissue under underneath that and essentially are reactivated right
Speaker 2: in the spot to then infect for the virus to
Speaker 2: that infect epithelial cells. Now, what I told you earlier
Speaker 2: was that when the virus infects epithelial cells, by default,
Speaker 2: it goes litic. It just replicates and it kills the cell.
Speaker 2: So why how would that cause cancer? That doesn't make
Speaker 2: any sense. Right. For viruses to cause cancer or contribute
Speaker 2: to causing cancer, they have to have something go wrong
Speaker 2: in their replication. And one of the things that needs
Speaker 2: to go wrong is that when it infects the cell,
Speaker 2: it has to have some aspect of its replication function crippled,
Speaker 2: either by mutation or by the cell having heightened antiviral
Speaker 2: responses or some other breakdown in replication. And so in
Speaker 2: EBV positive epithelial cancers, the virus is actually late so
Speaker 2: it's a Barrant process, right. Instead of replicatinglytically, it accidentally
Speaker 2: finds itself latent, and some of the latency proteins can
Speaker 2: be made, not all of the ones I described in
Speaker 2: the B cells, but usually those membrane proteins that keep
Speaker 2: the cells alive, the pro survival proteins. They're usually expressed,
Speaker 2: and then the EBNO one protein that maintains the viral
Speaker 2: genome is still expressed and together that cooperates with cellular
Speaker 2: mutations that arise in driving in this case, gastric tumor genesis.
Speaker 1: We know that this is a global virus, ninety five
Speaker 1: percent of people have it by the time they are adults.
Speaker 1: But is there geographic variation in this virus?
Speaker 2: Like are there.
Speaker 1: Different types of EBV? How much genetic variation is there
Speaker 1: in this virus?
Speaker 2: So most double stre into DNA viruses like EBB or
Speaker 2: other herpes viruses, compared to other viruses, are relatively stable genetically.
Speaker 2: They really don't mutate that much like influenza virus or
Speaker 2: sarscov two or any of the sort of acute respiratory viruses.
Speaker 2: Those RNA viruses don't tend to have the proofreading capacity
Speaker 2: typically in their polymerases when they replicate, and so they
Speaker 2: throw in errors every couple of thousand basis of nucleic acid,
Speaker 2: whereas it's much a much lower error rate in DNA
Speaker 2: replication for double strand DNA viruses. That being said, now
Speaker 2: we know as of about maybe seven or eight years ago,
Speaker 2: with genome sequencing technology developing and becoming cheaper, so we
Speaker 2: now have a couple of hundred of genomes sequenced, and
Speaker 2: what's emerged is a couple of things. So one is
Speaker 2: that the prototypical genomes we've been working with are representative
Speaker 2: actually of what you see across the world, so that's good.
Speaker 2: We know that there are two major types of EBV,
Speaker 2: so type one and type two is what they're called,
Speaker 2: and they vary in very specific genes, which is primarily
Speaker 2: the latency genes. So the majority of EBV in the
Speaker 2: world is type one. It's distributed across the world, and
Speaker 2: type two is more prevalent in Africa and in some
Speaker 2: parts of Asia, and so in some ways they're almost
Speaker 2: like two different viruses, but as far as we know,
Speaker 2: they really operate very similarly in terms of di cell
Speaker 2: infection and latency and reactivation. And everything else. So the
Speaker 2: other things that we learned from the genome sequencing experiments
Speaker 2: are that the genes that are important for virus entry,
Speaker 2: for example that could be vaccine targets, are relatively well conserved,
Speaker 2: so there's probably not a big concern about that variation
Speaker 2: like you have for flu for example, in hampering vaccine design.
Speaker 2: But there is some variation. But coming back to the
Speaker 2: geographic distribution, it turns out that one of the latency genes,
Speaker 2: called LMP one or latent number in proteen one, it
Speaker 2: varies quite a bit relatively, and one can see geographic
Speaker 2: distributions that link a particular LMP one genotype two regions
Speaker 2: of the world. We don't know what that means in
Speaker 2: terms of disease or spread or what have you, but
Speaker 2: it's been observed.
Speaker 1: So let's get into latency. Tell me more about what's
Speaker 1: going on with latency. What does it mean for a
Speaker 1: virus to go latent and what can trigger reactivation?
Speaker 2: Yes, awesome, Okay, it's my favorite topic. So latency in
Speaker 2: the case of EBV is sort of an active latency.
Speaker 2: It's not the kind of latency you might think of
Speaker 2: as the virus is sleeping and you know, don't wake
Speaker 2: it up. It is a form of infection in B
Speaker 2: cells that is the default form that when you acquire
Speaker 2: your EVV in the saliva. The initial infection in B
Speaker 2: cells leads to a series of eight viral proteins being expressed,
Speaker 2: and they're called latency proteins. Six of them are transcription factors,
Speaker 2: so they go into the nucleus and they turn on
Speaker 2: genes and turn off genes in the host genome, and
Speaker 2: two of them are membring proteins at the cell surface
Speaker 2: that activate cellular signaling pathways, and that mimics how that
Speaker 2: B cell would normally have responded to antigen or a
Speaker 2: foreign pathogen if it were normally doing its job. But
Speaker 2: EBB is sort of co opting that. So when the
Speaker 2: latency proteins are expressed, the cell that it infects, a
Speaker 2: B cell is just a resting cell. It doesn't divide
Speaker 2: unless it gets signals to divide. And so those nuclear proteins,
Speaker 2: the so called ebna's epstein bar nuclear energens, when they're expressed,
Speaker 2: the cells will start dividing, and they actually do so
Speaker 2: very rapidly, and that's mimicking what happens when a B
Speaker 2: cell would normally have seen some foreign antigen, and so
Speaker 2: that rapid proliferation occurs for a number of divisions. And
Speaker 2: at the same time, these membrane proteins that are activating
Speaker 2: the signaling pathways are telling the cells at all costs
Speaker 2: stay alive. And the reason that's important is that the
Speaker 2: process from a naive B cell maturing to becoming a
Speaker 2: plasma cell or a plasma blast, which is one of
Speaker 2: these antibodies secreting B cells or a memory B cell,
Speaker 2: that process is one in which the B cell is
Speaker 2: activated and rapidly proliferates, so like you have a lot
Speaker 2: of B cells around to ultimately be able to make
Speaker 2: antibodies to stop some pathogen from taking over. In that process,
Speaker 2: it's a little sloppy, so an enzyme comes on that
Speaker 2: actually damages the DNA, cuts the DNA and causes mutations
Speaker 2: in the DNA in the so called immunoglobular locus. So
Speaker 2: the genes that are going to make the antibodies get mutated,
Speaker 2: and that is the selection process by which the B
Speaker 2: cells go from having an antibody that initially recognized the
Speaker 2: pathogen to making a better and better, higher affinity antibody.
Speaker 2: That process is dangerous, right, there's all this DNA damage,
Speaker 2: there's all this churn and everything. So EBV actually mimics
Speaker 2: that process. And so if that cell is going to
Speaker 2: stay alive and still be an EBV infected cell when
Speaker 2: it comes out of it, it needs to tell the
Speaker 2: cells not to die. And then after a couple of
Speaker 2: rounds of division, it gets out into the proiffery into
Speaker 2: the blood as a memory B cell, and it shuts
Speaker 2: everything off and it becomes truly latent and quiescent. And
Speaker 2: the reason it does that is that all of those
Speaker 2: proteins that I told you about, the ebnas and the
Speaker 2: membrane proteins so called LMPs, those are highly immune dominant,
Speaker 2: and T cells are going to recognize them and kill
Speaker 2: those EBB infected cells. So it shuts everything off, gets
Speaker 2: into the blood and sits there. When that cell divides,
Speaker 2: it makes one protein, and the one protein is a
Speaker 2: protein called VNA, one that can facilitate the DNA replication
Speaker 2: just of the EBV genome, which is actually represented at
Speaker 2: this point as probably eight to ten copies so extra
Speaker 2: chromosomal circular copies of BBVDNA and then partitions them to
Speaker 2: daughter cells. Then if those cells find themselves in lumphoid
Speaker 2: tissue in the oral mucosa, and the actual antibody on
Speaker 2: the surface of that B cell recognize as an anigen
Speaker 2: that triggers the differentiation of the cell and the switch
Speaker 2: to litic replication, and so then the virus makes tons
Speaker 2: of particles and gets out. Now, it turns out that's
Speaker 2: not the only way it can happen. Like most herpes viruses,
Speaker 2: we often say stress can induce reactivation. What is stressed,
Speaker 2: so DNA damage from radiation as a stress, hypoxic environments so,
Speaker 2: low oxygen environments as a stress. In fact, some small
Speaker 2: molecules that are secreted by bacteria that might be in
Speaker 2: our oral microbiome as a stress can reactivate latent DBB.
Speaker 2: So it's not just the B cell receptor or the
Speaker 2: antibody on the surface of the B cells that needs
Speaker 2: to signal or recognize anagen to trigger reactivation. All of
Speaker 2: those different kinds of stresses can do it. A lot
Speaker 2: of this comes back to the idea that EBV is
Speaker 2: latently in all of us, in our B cells, and
Speaker 2: because it's in our B cells, those cells have a
Speaker 2: very specific function, which is that they have antibodies on
Speaker 2: the surface, and those antibodies could recognize other pathogens, they
Speaker 2: could recognize auto antigens, they could recognize nothing, And if
Speaker 2: they recognize nothing, that cell should have died, but EBV
Speaker 2: keeps it alive. And so that sort of central principle
Speaker 2: is what underlies the relationship between EBV and I think
Speaker 2: some of the cancers it's associated with, probably autoimmune diseases,
Speaker 2: and certainly how this symbiosis between EBV and the B
Speaker 2: cell why it works. Basically, so one about one in
Speaker 2: one hundred thousand of our memory B cells in our
Speaker 2: blood at any given time is EBB positive, So that
Speaker 2: ends up being probably tens of thousands of cells. And
Speaker 2: each of those else has a different specificity the B
Speaker 2: cell receptor on the surface of each of those cells.
Speaker 2: They might be for an E. Coli in your gut,
Speaker 2: They might be for the cold virus you had when
Speaker 2: you were for they might be for tetanus, vaccine anigen,
Speaker 2: they might be for some autoanigen. But because the virus
Speaker 2: is clas and most of the time everything's fine. So
Speaker 2: when we talk about EBV flaring up and this kind
Speaker 2: of thing, EBED is a barometer of our humoral immune response.
Speaker 2: It's like a little gauge of when things are okay
Speaker 2: and when things are imbalanced. And that's vague, but you
Speaker 2: can imagine that you could put specificity on it if,
Speaker 2: for example, it was a particular pathogen driving a particular
Speaker 2: clone of EBB that mimicked an autoanigen, like maybe that's
Speaker 2: what causes chogrin syndrome sometimes, or maybe that's what promotes
Speaker 2: ms sometimes. Right, it's all about the B cell.
Speaker 1: Talking more about autoimmune diseases and the potential role of EBV.
Speaker 1: What are the conditions that seem to have the highest
Speaker 1: support for an involvement of EBV And is it sort
Speaker 1: of that mechanism that you described or are there different
Speaker 1: mechanisms that are involved.
Speaker 2: I think there can really be two likely two mechanisms.
Speaker 2: One is what I just described, which is that because
Speaker 2: EBV finds itself in B cells, that's where it lives,
Speaker 2: if one of those B cells has an antibody that
Speaker 2: on its surface that is autoreactive, and that autoreactivity is pathogenic,
Speaker 2: then that would be a mechanism where the process that
Speaker 2: I described of how EBV latency proteins tell cells to
Speaker 2: proliferate keep them from dying expand clones. Right, that cell
Speaker 2: may actually come back through the lymphoid tissue and need
Speaker 2: to expand again, and if that happens, EBV is there
Speaker 2: to keep it alive. So that's for example, that's something
Speaker 2: that goes awry in Honchkin's umphoma. In this case, it
Speaker 2: could be in the case of certain autoimmune diseases. You
Speaker 2: can have B cells that are infected with an auto antibody.
Speaker 2: They expand, and perhaps they expand to becolm plasma cells
Speaker 2: that go to the bone marrow and just secrete antibody
Speaker 2: for a long period of time. And that could be
Speaker 2: this just a pathogenic auto antibody that you need to
Speaker 2: get rid of because that's what's causing a particular autoimmune condition.
Speaker 2: So that's one possible mechanism for how EBV could be
Speaker 2: involved in variety of autoimmune diseases. Another is what was
Speaker 2: proposed in the recent Nature paper about EBD's association with
Speaker 2: MS and molecular mimicry. What they found was that if
Speaker 2: they looked in the cerebral spinal fluid of MS patients
Speaker 2: where B cells should not be hanging out, but they
Speaker 2: found some, you know, enough to be able to then
Speaker 2: isolate them and pull out the antibody genes that are
Speaker 2: in each individual B cell express them, so make them
Speaker 2: in vitro in the lab and then ask well, what
Speaker 2: are these antibodies buying? And what they found was that
Speaker 2: about thirty percent of patients had antibodies that reacted with
Speaker 2: EBV antigens. And when they drilled down into which antigens
Speaker 2: were recognized, more often than not, it was this viral
Speaker 2: proteinv No one and that protein is known to play
Speaker 2: all sorts of games to avoid the immune system. So
Speaker 2: what does that mean? Why does that cause it? Why
Speaker 2: would that or could that cause ms? And it turns
Speaker 2: out that the small peptide region of v No one
Speaker 2: that's recognized by the antibody is virtually identical to a
Speaker 2: region of a protein that's expressed in neurons called gliocam,
Speaker 2: and that indicates that that specificity is one where just
Speaker 2: one amino acid difference is enough to shift you from
Speaker 2: recognizing a pathogen to recognizing your own protein. And so
Speaker 2: I think those are the two favored and plausible mechanisms.
Speaker 2: Is it the EBV positive B cells that are playing
Speaker 2: a role here, or is it this other mechanism of
Speaker 2: molecular mimicry, where the antibody response to an EBB protein
Speaker 2: could end up being what triggers reactivity with your neurons,
Speaker 2: which is bad. The question of how much in every
Speaker 2: case of MS or any other autoimmune disease does this contribute.
Speaker 2: I think that the serum in MS patients from the
Speaker 2: large military study is the strongest evidence yet of the
Speaker 2: requirement of EBV infection for developing MS, and I think
Speaker 2: that the Nature paper really strongly supports a potential pathogenetic
Speaker 2: mechanism of molecular mimicry could support the development of MS
Speaker 2: in some individuals. I think the idea that preventing EBV
Speaker 2: will prevent MS is going to require doing that experiment right,
Speaker 2: But I think the chances of that preventing MS are low.
Speaker 2: It may be that a subset of MS is EBV
Speaker 2: driven in some way, or is it really does require
Speaker 2: continued EBV infection, And again, whether it's related to how
Speaker 2: strongly you're able to prevent autoreactive T cells and B
Speaker 2: cells from developing versus how well you keep your EBV
Speaker 2: in check. That's something that the field is really deeply
Speaker 2: interested in figuring out over the next five to ten years.
Speaker 1: So besides this MS research that's been in the news lately,
Speaker 1: EBV has also, I feel like, made headlines for its
Speaker 1: potential involvement in long COVID. What do you think about that,
Speaker 1: what research has been done on that, and do you
Speaker 1: think that it's a plausible link.
Speaker 3: I think that the link between EBV and long COVID
Speaker 3: likely has to do with this idea that EBV infection
Speaker 3: latent infection in B cells is sort of a barometer
Speaker 3: of your humoral immune system, and so when things are.
Speaker 2: A little off balance, either because you've got coinfection and
Speaker 2: huge amount of cytokine is being released either systemically or
Speaker 2: locally in some lymphoid tissue, that this can trigger EBV reactoration,
Speaker 2: and depending on how well the patient is doing in
Speaker 2: terms of maintaining their EBV specific T cell responses in
Speaker 2: EBV immunity, that can essentially be a mono like situation
Speaker 2: or in any event, can cause a lympho proliferation and ultimately,
Speaker 2: you know, some disease associated with that that could overlap
Speaker 2: with some of the long COVID symptoms. So I think
Speaker 2: fatigue being the major one that has been linked when
Speaker 2: EBV DNA is detected in the blood. That indicates that
Speaker 2: there's really a significant imbalance in these EBV infected B cells.
Speaker 2: And so whether that is again simply a barometer of
Speaker 2: the underlying immune health of that individual, or is contributing
Speaker 2: to some of the symptoms like fatigue in long COVID,
Speaker 2: I think just warrants further study.
Speaker 1: So I want to end the part one of this
Speaker 1: interview with a question that is very general and hopefully
Speaker 1: very fun. Do you have a piece of favorite trivia
Speaker 1: for either EBV or justviruses in general?
Speaker 2: Yes, okay. EBV was discovered in nineteen sixty three to
Speaker 2: nineteen sixty four by Anthony Epstein, who was an assistant
Speaker 2: professor in the UK and his graduate student, yvon bar
Speaker 2: and he had seen a talk in sixty three from
Speaker 2: Dennis Burkett, who was an Irish missionary surgeon working in Uganda,
Speaker 2: who had characterized this large draw tumor that is the
Speaker 2: most prevalent pediatric tumor in subsern Africa. And at the
Speaker 2: time we knew that other animals could be infected with
Speaker 2: certain viruses that caused cancer, but no human tumor virus
Speaker 2: had been discovered, and so Dennis Burkett presented this study
Speaker 2: where he mapped the epidemiology of this cancer. This burke
Speaker 2: at lymphoma across Africa and it was almost coincident with
Speaker 2: where malaria was holoandemic. Epstein was wrapped and was certain
Speaker 2: that there was a virus, probably transmitted by the mosquito
Speaker 2: that was also transmitting hilaria that would cause this lymphoma,
Speaker 2: and so they set up a collaboration where specimens from
Speaker 2: the lymphoma will be sent from Kampala to London, and
Speaker 2: over months and months of investigation, no virus was found.
Speaker 2: And so the twenty sixth biopsy was being flown to
Speaker 2: London and there was fog in the city and the
Speaker 2: flight was diverted to Manchester and the sample sat overnight
Speaker 2: and was brought to the lab and the liquid that
Speaker 2: it was in was cloudy, and so he thought, oh gosh,
Speaker 2: it must have been contaminated with bacteria. But let's take
Speaker 2: a look anyway, and when you look under the microscope
Speaker 2: he saw that the cloudy stuff wasn't bacteria, but it
Speaker 2: was cells and some cells had been had sloughed off
Speaker 2: of the tumor. And at the time, nobody knew how
Speaker 2: to grow lymphocytes, so there was no culture system for lymphocytes.
Speaker 2: But nevertheless, Yvonne bar tried a bunch of different conditions
Speaker 2: and was able to successfully grow the cells that had
Speaker 2: slept off from the tumor, and a couple of weeks
Speaker 2: later they had enough cells, and sure enough, in about
Speaker 2: one out of one hundred cells chalk full of herpes
Speaker 2: virus like particles. And that was it, that was the discovery.
Speaker 2: And he got up and went outside and walked around
Speaker 2: the building and came back and looked again, and sure enough,
Speaker 2: the cell cells are chock full of herpes virus like particles.
Speaker 2: So he was wrong about what kind of virus it
Speaker 2: would be. It wasn't transmitted by the mosquitos, but he
Speaker 2: was absolutely right that there was a virus in those cancers.
Speaker 2: That story of the discovery of the virus, as told
Speaker 2: by Anthony Epstein at the fiftieth anniversary of the discovery
Speaker 2: about eight years ago, is my favorite piece of virology trivia.
Speaker 1: That is such a fantastic story, and it must have
Speaker 1: been so cool to get to hear it directly told
Speaker 1: by the man himself. So we're going to take a
Speaker 1: quick break here, and then when we get back. I
Speaker 1: want to hear all about what virology as a career
Speaker 1: is like and any words of wisdom you may have
Speaker 1: for people who might just be starting out on this journey.
Speaker 1: Welcome back everyone, All right, so let's talk about virology
Speaker 1: as a career. What it's like to be a virologist.
Speaker 1: What got you interested in EBV? Did you know all
Speaker 1: along that you wanted to study viruses?
Speaker 2: I knew I wanted to study viruses, and I was
Speaker 2: always interested in studying viruses that caused cancer. So it
Speaker 2: turns out my dad's a virologist, which is maybe not
Speaker 2: the most common route that people get into the field,
Speaker 2: but in my case, when I was a kid, I
Speaker 2: used to go to American Society for Virology meetings on
Speaker 2: college campuses in the summer and hang out and eat
Speaker 2: pizza and you know, meet graduate students and then meet virologists.
Speaker 2: And then as I got older, I would go as
Speaker 2: a high school student, and I started getting into the science.
Speaker 2: I was always a math and science nerd, and so
Speaker 2: I really became interested in biology and started to ask
Speaker 2: questions at these meetings. And then late in my high
Speaker 2: school career had some experience in doing some microbiology research.
Speaker 2: And then when I started in college, knew I wanted
Speaker 2: to work on viruses, and so found the virology lab
Speaker 2: on campus, and actually it was a herpe simplex virus lab.
Speaker 2: So I started working with HSV from early on and
Speaker 2: how the virus inter cells and the glycoproteins that uses
Speaker 2: the receptors and this kind of thing. And so junior
Speaker 2: to senior year transition I worked at the CDC. I
Speaker 2: had an opportunity to do an internship there and worked
Speaker 2: in the herpes virus section with the chief named Phil Pellett.
Speaker 2: The lab was studying all different herpes viruses and around
Speaker 2: that time a new virus had been discovered called KSHB
Speaker 2: or capcy sarcoma associated herpes virus, and so they were
Speaker 2: really keen to just understand the basics, you know, like
Speaker 2: let's grow this virus and let's purify it, and let's
Speaker 2: figure out what proteins are in it and how it
Speaker 2: inter cells and all this basic stuff. And so I
Speaker 2: had a hugely impactful experience there, not just from the
Speaker 2: science and the kind of science we're doing, but Phil,
Speaker 2: after you know, we finished in the lab, would would
Speaker 2: stay and we'd chat about the future, you know, what
Speaker 2: I was going to do, and where I might be
Speaker 2: interested in going to graduate school, and what questions to
Speaker 2: work on, and really had an opportunity to think about
Speaker 2: that carefully, and so he suggested EBV. He said, this
Speaker 2: is if you want a big challenge and you want
Speaker 2: to understand viruses that can cause cancer, you should work
Speaker 2: on EBV. There number of labs in the country that
Speaker 2: were really exceptional in studying it. So I wrote to
Speaker 2: them and applied to graduate schools and ended up going
Speaker 2: to graduate school to work on EBV.
Speaker 1: Basically, so, as a professor, you have to do so
Speaker 1: many things like that that one word covers a lot
Speaker 1: of different you know, responsibilities you have to do each
Speaker 1: You have to write grants, you have to do the research,
Speaker 1: you have to manage a lab, you have to advise
Speaker 1: grad students and everything you know in between. Are there
Speaker 1: any parts of your job that you absolutely love or
Speaker 1: parts that you could easily give up and not look back.
Speaker 2: The part that I absolutely love is what got me
Speaker 2: into it from the beginning, and it's seeing new data
Speaker 2: and seeing new discoveries made that no one's ever seen before. Right,
Speaker 2: So that bug that sort of fire in the belly
Speaker 2: to be able to see this new discovery and want
Speaker 2: to ask the next questions and figure out the mechanism
Speaker 2: and just develop a project. That that's really what I love.
Speaker 2: And like you said, though, along the way, all of
Speaker 2: the other benefits features of being a professor, you know,
Speaker 2: come with you. And I have to say I, in
Speaker 2: my training, I did not have an opportunity to do
Speaker 2: as much mentoring as maybe others, and that is something
Speaker 2: that I do really love. I love doing that in
Speaker 2: the context of the lab, you know, so training graduate
Speaker 2: students or undergraduates that come in the law post docs,
Speaker 2: and also doing that the context of faculty mentoring, and
Speaker 2: you know, really helping junior faculty get get started and
Speaker 2: transition through tenure and all of those challenging spots in
Speaker 2: their career. And you know, teaching is something that I
Speaker 2: love when I'm doing it, but I don't love thinking
Speaker 2: about having to do it. I'm telling you about a
Speaker 2: lot of things I love. What do I hate about
Speaker 2: this job? I thought I've been thinking a little bit
Speaker 2: about that. I don't. I don't hate writing grants. I
Speaker 2: think I actually think writing grants are really useful as
Speaker 2: an exercise to uh distill your ideas into a digestible
Speaker 2: set of uh, you know, future experiments and you know,
Speaker 2: setting up rationale for why you're doing what you're doing.
Speaker 2: Don't like the process of you know, waiting and you
Speaker 2: having it reviewed and biting your nails and all that stuff.
Speaker 2: But I do like writing the grants because of what
Speaker 2: it does for the science. I don't love where things
Speaker 2: are right now with academic publishing. I think they could
Speaker 2: be improved in a number of ways. I think that
Speaker 2: one of the aspects that you know, a lot of
Speaker 2: folks talk about, and I agree with this, is that,
Speaker 2: you know, really linking our sort of productivity and our
Speaker 2: worth to the impact factor of the journal that we
Speaker 2: publish our papers in is not not appropriate. And how
Speaker 2: to get away from that when we evaluate faculty candidates
Speaker 2: or people coming up for ten year promotion or have
Speaker 2: you is tough, but I think we try our best
Speaker 2: to do that in terms of evaluating the actual impact
Speaker 2: of the work and the you know, the rigor of
Speaker 2: the science and the reproducibility of the science was often
Speaker 2: isn't something that that comes into play, despite how challenging
Speaker 2: that issue can be. So I think if there was
Speaker 2: one area that I don't love. It's kind of the
Speaker 2: space of navigating the publication system.
Speaker 1: So on the alumni section of your lab website, I
Speaker 1: see that you've graduated students that have gone into very
Speaker 1: different careers, from government positions to industry, to medicine and others.
Speaker 1: So besides academia, what other careers do you think that
Speaker 1: a master's of science or a PhD in microbiology would
Speaker 1: set you up for?
Speaker 2: Yeah? Absolutely, I think a lot of different careers. I
Speaker 2: think that we train critical thinkers, we train effective communicators,
Speaker 2: We train folks to solve difficult problems by working in
Speaker 2: and valuing diverse perspectives on teams that will get you there.
Speaker 2: And that skill set describes as you can imagine a
Speaker 2: lot of different industries, right, so obviously or learning how
Speaker 2: to do that in the context of pipetting and whatnot.
Speaker 2: So doing that in science in industry, you know, is
Speaker 2: the most logical place to go next from the point
Speaker 2: of view of if you love the science right aspect
Speaker 2: of it, if you love the communications aspect of it,
Speaker 2: or if you love the entrepreneurship aspects of it, then
Speaker 2: there are sort of slightly different paths that you can take.
Speaker 2: So I mean the industry now. You know, it's interesting
Speaker 2: when I think back to even my time as a
Speaker 2: post doc, the opportunities in industry were relatively limited to
Speaker 2: sort of big pharma or basically big biotech or startups,
Speaker 2: but you know, the relative risk there was still pretty high.
Speaker 2: And that array of opportunities to be a PhD or
Speaker 2: master's level scientist in biomedical research in industry is now
Speaker 2: incredibly diverse. And it's not restricted only to Boston and
Speaker 2: the Bay Area OURTP where we are here obviously, you know,
Speaker 2: is full of companies developing all through that spectrum. So
Speaker 2: I think a lot of folks are really excited about
Speaker 2: moving into industry where they can sort of see the
Speaker 2: kinds of basic discovery type work we do here translated
Speaker 2: into drugs or therapies in some way, and when you're there,
Speaker 2: you have an opportunity to really expand and explore other
Speaker 2: aspects of that process. Right, So, whether it be liaising
Speaker 2: with clinicians as a medical science lise on, whether it
Speaker 2: be developing writing nbas and doing really more science communication,
Speaker 2: or having an opportunity to shift and do more business
Speaker 2: development and entrepreneurship, you know, there are a lot of
Speaker 2: opportunities just in you know what now is kind of
Speaker 2: biotech and pharma that really broad industry. And then, like
Speaker 2: you said, some of the folks from my lab have
Speaker 2: gone on to policy fellowships and really working to impact
Speaker 2: the way that our government and you know, at any
Speaker 2: level really thinks about and communicate science. And I think
Speaker 2: that's obviously very much needed these days. And you know,
Speaker 2: I think there are certainly still other areas that you're
Speaker 2: competitive for consulting or patent law or what have you. So,
Speaker 2: so really a wide range of you know, of opportunities
Speaker 2: in what you can do with their master's or a PhD,
Speaker 2: and the sort of resilience and you know, other things
Speaker 2: that come from doing your PhD really set you up
Speaker 2: nicely for any of those kinds of careers.
Speaker 1: What advice would you give someone who is interested in
Speaker 1: biology broadly but isn't sure exactly what they want to
Speaker 1: do or what's available to them, And what do you
Speaker 1: think are the most important factors to consider when thinking
Speaker 1: about the career that you want to have whatever relates
Speaker 1: to in biology.
Speaker 2: Yeah, so I think even starting to think about this
Speaker 2: at an early age, you know, high school or even before,
Speaker 2: I would say seek out a mentor seek out someone
Speaker 2: that you can talk to about science, about being a scientist.
Speaker 2: There are a lot of especially in the COVID era,
Speaker 2: a lot of societies like ASB and ASM have been
Speaker 2: doing really like open webinars and podcasts and communication events
Speaker 2: to encourage young people that are interested in biology and
Speaker 2: interested in science to come not just learn about what
Speaker 2: science we do in the lab every day, but like
Speaker 2: what you know, what the field really is like and
Speaker 2: what the path is going to look like, right, because
Speaker 2: I think a lot of folks don't know what for example,
Speaker 2: graduate school is like you know from high school or
Speaker 2: even college. It's like some people think it's just the
Speaker 2: alternative to medical school or something, whereas you know, what
Speaker 2: I would suggest is that if you can find a scientist,
Speaker 2: try to find an opportunity to do research in some way.
Speaker 2: They're more and more even virtual options for this because
Speaker 2: of what's happened with the pandemic, where where you can
Speaker 2: engage with the scientists in the lab and maybe do
Speaker 2: a computational project or just reading and learning about a topic.
Speaker 2: And ultimately I think what you want to try to
Speaker 2: get to is to be involved in doing an experiment
Speaker 2: and seeing the discovery. If that bites you, if you
Speaker 2: see something no one's ever seen before, whether you did
Speaker 2: it with your own hands or you're working with a
Speaker 2: graduate student or somebody you know in the lab and
Speaker 2: you see something, and if that bites you and you realize, oh,
Speaker 2: I could do this and see things nobody's ever seen
Speaker 2: before and really develop that and come up with new
Speaker 2: experiments to test new hypotheses. You know, that is when
Speaker 2: you know that being a scientist might be for you.
Speaker 1: So you talked about one way that you wish academia
Speaker 1: could be better, right in the context of publishing and
Speaker 1: the way that we evaluate certain candidates or the way
Speaker 1: that people maybe evaluate their own self worth in academia.
Speaker 1: What would you say about grad school? What are the
Speaker 1: ways that in general graduate school in biology or microbiology
Speaker 1: could do better.
Speaker 2: Graduate school is changing a lot in front of our eyes.
Speaker 2: And when I got to do about fifteen years ago,
Speaker 2: most of the programs, I would say were relatively conservative
Speaker 2: and kind of old school and their approach, which was
Speaker 2: the mentality that students were workers that had to have
Speaker 2: pressure sort of applied to have them perform and produce things.
Speaker 2: And that is for obvious reasons. The kind of thing
Speaker 2: that leads to really significant burnout and mental health challenges
Speaker 2: that certainly still exist in graduate education today. But I
Speaker 2: think what I'll say is we're we're a number of
Speaker 2: things have happened over the years, at least here at Duke,
Speaker 2: where we've recognized a lot of how we were training
Speaker 2: students and basically blind spots and what we were missing,
Speaker 2: especially in terms of what we were just talking about before,
Speaker 2: which is where are you going to go? Right? Are
Speaker 2: you going to go into academia? Are you going to go,
Speaker 2: you know, into industry, You're going to be a scientist,
Speaker 2: You're going to have a different career path. And when
Speaker 2: you simply look at the numbers, you see that about
Speaker 2: fifteen to twenty percent of our graduates wind up in
Speaker 2: academia and fifty percent are in industry. Right, So there
Speaker 2: was at the time, you know, would people would say
Speaker 2: alternative careers or something like that to academia, which is ridiculous,
Speaker 2: right with the majority of people are going into other careers.
Speaker 2: So it was that realization that happened maybe ten or
Speaker 2: so years ago here at the graduate school. A lot
Speaker 2: of effort was put into rethinking, reimagining graduate education around
Speaker 2: and you know, having a PhD, what what you need
Speaker 2: to be trained for in the biomedical research you know,
Speaker 2: workforce and and what are the skills that are most
Speaker 2: important broadly? And number one is problem solving, creative thinking, resilience, communication,
Speaker 2: to a broad audience, to an arrow audience, uh, writing,
Speaker 2: All of these things really are are the foundation being
Speaker 2: able to do this in an environment that is respectful, diverse,
Speaker 2: pro student. But you know, it's just a rethinking of
Speaker 2: uh you know, what the goals are and how and
Speaker 2: how you get there and I think you know, partnering
Speaker 2: with one another as you know, it's a mentor mentee relationship,
Speaker 2: but it's also one where we're colleagues, right, and seeing
Speaker 2: each other in that way and being respectful and and
Speaker 2: and challenging each other, right, I mean that is part
Speaker 2: of the process, but you know, seckful way.
Speaker 1: I have one last question for you, and that is
Speaker 1: to ask you what you hope this next year brings
Speaker 1: in terms of EBV research or other research or just
Speaker 1: general personal goals for you and or for your lab.
Speaker 2: So for the lab, I'm really excited about the area
Speaker 2: of science that we've been in for a couple of
Speaker 2: years now, which is I would generally call a heterogene
Speaker 2: heterogeneity of infection. So if you infect cells, they don't
Speaker 2: all behave the same way, So we generally lump things
Speaker 2: together sometimes and say infected and uninfected, or you know
Speaker 2: that kind of thing. And I've always been really interested
Speaker 2: in temporal dynamics, like how things change over time after infections,
Speaker 2: but also what's the difference between cell A and cell
Speaker 2: B And if you infect a million cells, are they
Speaker 2: all bonding the same way? The answer, the short answer
Speaker 2: is no, not at all. And so we've been using
Speaker 2: technology called single cell RNA sequencing as one method to
Speaker 2: be able to see those differences, whether it be during
Speaker 2: latency or liticcary activation of the virus, or different tumor
Speaker 2: cell lines and different settings. And we've we've published a
Speaker 2: paper on this already and have a couple more coming
Speaker 2: out this year that are really telling us just about
Speaker 2: how different the outcomes of viral infection can be at
Speaker 2: the single cell level and what that might mean then
Speaker 2: for disease, for latency, establishment, for therapeutic approaches, and and
Speaker 2: you know, I think is uh, it's really an exciting
Speaker 2: time to be studying UBV. As you know, the first
Speaker 2: doses of the moderna EVV vaccine have have gone into arms,
Speaker 2: and so everybody's excited to see how how that does
Speaker 2: in terms of impact mono and also EBV replication and development.
Speaker 1: Thank you so much, doctor Leftig. That was such a
Speaker 1: fascinating interview and I definitely gained a lot more respect
Speaker 1: and awe for this virus and what it can do.
Speaker 1: If you would like to learn more about the super
Speaker 1: cool work that doctor Leftig and his lab is doing,
Speaker 1: I will post a link to his lab website on
Speaker 1: our website This podcast will kill You dot com. Speaking
Speaker 1: of websites, our website is also where you can find
Speaker 1: all kinds of things like the sources for all of
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Speaker 1: you enjoyed this fora into EBV, and a special thank
Speaker 1: you to our wonderful, generous patrons. We appreciate you so much.
Speaker 1: We have got a brand new episode on a brand
Speaker 1: new topic coming out next week, so until then, keep
Speaker 1: washing those hands.