#0 – What Are Viruses?

00:00:07: There's this really great quote from Peter Medova, was a British biologist who once said that the virus is a piece of bad news wrapped up in protein.

00:00:16: And that describes viruses very well.

00:00:46: Hello and welcome to episode zero of Virological.

00:00:50: This episode was recorded on January fourth in New York City.

00:00:54: My name is Florian Kramer.

00:00:55: I'm a professor at the Department of Microbiology at the Icans School of Medicine at Mount Sinai in New York.

00:01:01: And I'm also the director of the Ludwig Boltzmann Institute for Science, Outreach and Pandemic Preparedness at the Medical University of Vienna in Austria.

00:01:10: And also the director of the Ignaz Semberweis Institute for Infection Research, which is also located in Austria.

00:01:17: Because of recent developments including the pandemic, I thought it might be a good idea to start a podcast that provides some general and basic information about viruses, but also about vaccines, about immunity.

00:01:31: And the idea is to record short episodes, maybe fifteen minutes, to cover different viruses every week.

00:01:39: I would like to cover viruses that are medically relevant, but I also would like to spread some virus trivia and to cover current events.

00:01:46: For example, if an outbreak happens, or if you have a strong flu season, like this year.

00:01:52: But with this episode zero, I will provide some basics about viruses and virology in general.

00:01:58: and that may take a little longer than fifteen minutes and maybe we will also have some future episodes that are longer that cover immunity, vaccine development or similar general topics.

00:02:11: But again today I'm going to start with some basic things about viruses.

00:02:15: So the first question is what are viruses?

00:02:18: Viruses are a combination of genetic information that codes for a protein and that protein or several of them encapsulate the nucleic acid that has this genetic information.

00:02:33: Often, but not always, viruses also include a lipid layer for protection, but it can just be protein on the outside.

00:02:41: And that's the basic building plan of a virus.

00:02:44: Of course, this can get much more complicated, but in general, just nucleic acid and protein, those are the most simple viruses.

00:02:54: Viruses are very small usually between eighty to hundred twenty nanometers in diameter.

00:03:00: but there's a lot of variation there and we'll talk a little bit more about very small and very large viruses later.

00:03:07: but just to make a comparison in terms of size a human hair is about eighty thousand to hundred thousand nanometers in diameter.

00:03:17: so viruses in comparison are really very small and they're basically invisible even in a microscope.

00:03:24: you can only see them and visualize them with an electron microscope.

00:03:28: As I mentioned, viruses are usually a combination of genetic material and protein and maybe lipids.

00:03:34: And there's this really great quote from Peter Medovar, was a British biologist who once said that the virus is a piece of bad news wrapped up in protein.

00:03:44: And that describes viruses very well.

00:03:46: Although I have to say that it can be bad news, but it doesn't have to be.

00:03:51: Not all viruses are bad.

00:03:52: Some are actually beneficial and I'll give you some examples later.

00:03:57: Viruses were discovered in the end of the nineteenth century.

00:04:01: The first virus that was discovered and described was the Bacomosaic virus or DMV.

00:04:07: Back then it was known already that bacteria could cause infections and disease, but it was also known that they could be removed from liquids via filtration.

00:04:20: The discovery of the tobacco mosaic virus goes back to Dimitri Ivanovsky who was working on diseases of tobacco plants on Crimea.

00:04:31: And so he mashed up leaves from deceased tobacco plants and then filtered that liquid through porcelain filter.

00:04:39: and then he put the filtered liquid back onto the tobacco plants.

00:04:43: And they got the disease again even though the material was filtered and that made it clear to him that the disease he was observing wasn't really caused by bacteria but by something smaller.

00:04:53: And these experiments were repeated a few years later and reproduced by Martino's Beijering in the Netherlands.

00:05:01: and he basically could show the same that he could filter these mashed up leaves, the juice from these mashed up leaves and still pass the disease on to new plants with this filtered material.

00:05:14: And so he concluded that the pathogen that caused the disease has to be very small and he called the pathogen virus.

00:05:22: or filtrable virus.

00:05:24: and virus is a Latin term which basically just means slime or chews or poison.

00:05:30: and that was basically the beginning of modern virology as a science.

00:05:36: Now viruses are not living beings, they're not alive at all.

00:05:40: Of course one could argue about that and I think virologists would like to see them as living beings but they do not fulfill all criteria of life.

00:05:51: So first they don't have a metabolism and second they cannot proliferate on their own.

00:05:56: They always need a host organism, basically a living organism which they can use for proliferation.

00:06:03: So in a way they are the perfect parasite.

00:06:05: And this is very different from bacteria which can also cause disease of course, but they don't necessarily need a host.

00:06:13: You can grow them in a nutrient-rich broth, but... That doesn't work with viruses.

00:06:19: They really need a living cell, a living organism to proliferate.

00:06:23: If you would just put them into a nutrient-rich broth or a sugar solution, nothing would happen.

00:06:28: The viruses basically wouldn't proliferate.

00:06:31: They need a living cell.

00:06:33: Depending on the virus, these living cells may be quite different.

00:06:37: So some viruses infect bacteria, some viruses infect archaea, some viruses infect fungi.

00:06:44: some in fact plants.

00:06:46: and then there's plenty of viruses that infect animals all kinds of different animals unfortunately including humans.

00:06:53: and the idea is that for every species on this planet for every species of living being there are at least ten different viruses that are specific for that species.

00:07:03: and that means that there are a lot of different viruses out there.

00:07:06: And most of them are actually completely harmless for humans.

00:07:10: And there is currently a large effort ongoing in virology to discover and identify all these viruses and map their diversity to get a better idea of how many they're actually out there and which ones we have to be careful about.

00:07:24: So viruses can be divided into different groups, usually according to what we call the Baltimore classification, where viruses are classified according to their genome and the properties of their genome.

00:07:37: So this classification was introduced by David Baltimore, a virologist who I believe got the Nobel Prize in nineteen seventy-five for his work on retroviruses.

00:07:47: and viruses that can cause cancer.

00:07:50: Unfortunately, he passed away in twenty twenty five.

00:07:53: He was also really a good fly fisherman, but basically came up with this classification scheme and that classifies viruses according to what their genome is made of.

00:08:04: I don't want to go into too much detail here, but there are viruses that have a DNA genome, which can be either single stranded or double stranded.

00:08:14: So humans also have a DNA genome.

00:08:16: These viruses have genome that's made of the same material.

00:08:19: Then there's viruses that have an RNA genome.

00:08:22: Again, this can also be single-stranded or double-stranded.

00:08:27: And then there are super interesting viruses that have an RNA genome, which they transform into a DNA genome in the host cell.

00:08:35: And they're called retroviruses.

00:08:36: And HIV is one such a retrovirus.

00:08:40: Once we talk about the different viruses in the different episodes, I will always specify what type of genetic information the specific virus has.

00:08:49: Viruses also come in different shapes and sizes.

00:08:52: There are some very small viruses that are just about forty nanometers in size or even smaller.

00:08:58: There are also very large viruses.

00:09:00: That's a set that come in very different shapes.

00:09:04: A very common and simple shape is basically a virus where The genome is packaged into a spherical protein shell, which we typically call an envelope.

00:09:15: And in many cases, this protein shell has a symmetrical and regular order, almost like a volleyball or a soccer ball.

00:09:25: An example for this are bichordner viruses.

00:09:28: like bolioviruses or rhinoviruses, they're pretty small, they're round and they have a symmetric regular order.

00:09:34: Then there are other viruses which are also spherical but less symmetrical.

00:09:39: An example for that are ortomixoviruses like influenza virus and they can be spherical but maybe also a little bit egg-shaped, sometimes a little bit elongated, sometimes they're a little bit smaller, sometimes they're a little bit bigger.

00:09:52: so they're not.

00:09:53: they're not really regular in size and we call this pleomorphic.

00:09:58: Then there are viruses that are filamentous, so really elongated, almost like a worm, and they are called filoviruses, and Ebola virus is an example for a filovirus.

00:10:11: They still have a very small diameter, but can be one to two micrometers long, so this is thousand to two thousand nanometers long, so they're much longer than their thickness in diameter.

00:10:22: Viruses that infect bacteria, for example, which we call bacteriophages because they... in a way, eat bacteria, may look like a little moon lander with a head and then some legs and they really use these legs to attach to the bacteria and infect the bacteria.

00:10:40: So that's a very interesting shape.

00:10:43: Then there are viruses like raptor viruses that are bullet shaped and one example is the rabies virus which also has this bullet shape and In this case it really fits because of course rabies is a very dangerous virus.

00:10:58: What has to be said in general is that not all viruses are problematic or cause issues.

00:11:05: Most viruses are actually harmless for humans and as I mentioned earlier there are even viruses that are beneficial to us.

00:11:11: It is important to understand that we have co-evolved with a lot of different viruses and specifically retro viruses have during our evolution not just as humans, but even before that as mammals, deposited their genome into our genome.

00:11:27: And they're not part of our genome.

00:11:29: There's a lot of retroviral sequences in our genome.

00:11:34: And most of them are not even forming infectious particles anymore.

00:11:38: Many of them don't do much.

00:11:40: They just tag along as part of our genome when we reproduce.

00:11:45: And one of these viruses, which ended up in mammalian genomes a long time ago, actually carried a gene for a protein that's called syncytine.

00:11:54: And that protein is essential for the formation of the placenta.

00:11:58: So we basically did it the other way around.

00:12:00: We hijacked the virus in that case, and there would be no mammals without this virus, because if we wouldn't have that sequence, there would be no placenta, and that would mean there would be no mammals.

00:12:14: So it's not always the case that only the virus profits or benefits from the infection.

00:12:19: In this case, it was basically the host, us, who profited from the integration event.

00:12:27: Viruses can also be used for all kinds of other things in biotechnology, for example, for the production of recombinant proteins, for gene therapy, but also in agriculture or forestry as an organic pesticide.

00:12:41: Baccala viruses are one example here.

00:12:44: These are large DNA viruses that are completely harmless for humans, but they infect and kill moths.

00:12:51: And they're used to control apple worms, for example, or insects that damage forests.

00:12:57: So there's a lot of different uses for viruses.

00:13:02: Also, there are more and more bacterial infections with multi-resistant bacteria that are really hard to treat.

00:13:09: And because this bacteria resistant to most of the antibiotics that we have at hand and this can in many cases end deadly.

00:13:19: and one new approach to to fight these infections now to use bacteriophages so viruses that infect and kill bacteria.

00:13:30: and that's a big development and an interesting development recently to basically have bacteriophages viruses that infect bacteria to treat these bacterial infections.

00:13:42: It's a very promising approach that becomes more and more important since we have more and more bacterial resistance.

00:13:49: And this is on the rise, so that's an important use for viruses.

00:13:53: Finally, viruses are also used to treat cancer and kill cancer cells.

00:13:57: Specifically, there's one such virus on the market in the United States, but there's also many different viruses in development as on colitis.

00:14:06: cancer therapies.

00:14:08: So in conclusion viruses are not always the bad guys but of course very often they can cause disease in humans or domesticated animals in wildlife.

00:14:20: And as I mentioned viruses always need cells to proliferate.

00:14:24: and I would like to describe the typical life cycle of a virus when it starts to attach to a host cell and then replicates and then gets released from that host cell.

00:14:36: So first the virus has to attach to the cell and in order to infect it.

00:14:41: And that usually happens via the surface proteins of the virus, which typically bind or attach to specific structures on the cell surface of the host cell.

00:14:52: And depending on the cell and the virus and the species, the structures that we call receptors can be vastly different.

00:15:01: So often they are sugar structures on the cell surface or their proteins can be very different proteins.

00:15:08: One example that is now widely known is SARS coronavirus II that has a spike protein on the surface and with the spike protein it binds to protein on our cell surface.

00:15:22: that's called ACE II or angiotensin converting enzyme II.

00:15:27: That's basically the receptors.

00:15:29: the virus comes in with its spike protein.

00:15:32: it attaches to that protein on the cell surface and that's how it attaches to our cells.

00:15:37: So the virus attaches to the cell surface and then in the next step the virus has to make it into the cell and there are multiple ways to achieve that as well.

00:15:47: More precisely, more specifically, it's not the virus that has to make it into the cell.

00:15:52: It's the genome of the virus.

00:15:54: It's genomic information that has to make it into the cell.

00:15:57: And as I said, there are multiple ways for viruses to do that, but especially for viruses that infect human cells or animal cells, the cell often does this job for the virus and actively takes it up by a little vesicles that we call endosomes.

00:16:12: So again, the virus starts the infection by binding to the cell surface and then the cell membrane forms an indentation and the small vesicle forms around the virus and the cell actively takes it up.

00:16:27: So it's the cell itself that does this, unfortunately.

00:16:30: And these vesicles then travel inside the cell, they mature, typically their pH changes, they turn acidic, and in many cases that then causes changes in the virus structure.

00:16:45: What then often happens is that the virus membrane, so basically the protein and the lipid on the surface, fuses or merges with the vesicle membrane.

00:16:57: Basically the inside of the virus is emptied out into the cell and that's where the genome was, right?

00:17:05: Inside the virus.

00:17:07: Now the genome that was inside the virus is all of a sudden inside the cell and that's of course a problem.

00:17:14: So there's other pathways.

00:17:15: how the virus can get in.

00:17:17: the virus genome get into the cell as well but this one is very common.

00:17:22: So as soon as the viral genome is in the cell we have a problem.

00:17:26: The cellular machinery recognizes the genome and it starts to read it and it starts to make viral proteins.

00:17:34: And so these new viral proteins then also amplify the viral genome and you get more and more genome and more and more viral proteins.

00:17:41: And then new viruses are formed which then usually leave the cell via the cellular membrane, which is a process that is called viral budding.

00:17:52: Also other mechanisms for leaving the cell.

00:17:55: In some cases the cell just bursts and the new viruses are released.

00:17:59: That's very common for viruses that infect bacteria for example.

00:18:03: But there's also multiple other pathways for the virus to exit the cell.

00:18:08: So in principle the virus hijacks the cell, takes over control and transforms the cell into a virus factory.

00:18:18: That is bad of course because that means a lot of viruses are produced, a lot of new viruses are produced that then go on and infect more cells and the infection continues in our body.

00:18:29: That is often what happens but that's not always the case.

00:18:34: There are also some viruses that infect the cell and then hide in it often for a very long time.

00:18:39: that can lead to persistent or chronic infections and there are a number of ways how viruses can achieve that.

00:18:46: Herpes viruses are good examples for that.

00:18:49: They're really good at this.

00:18:50: They enter a cell and then they deposit their DNA genome in the cell nucleus.

00:18:56: So it's not becoming part of our genome but it's sitting right there next to our genome, next to our chromosomes and it kind of forms a little extra chromosome.

00:19:05: basically a mini chromosome that's just sitting there for years in the nucleus of the cell.

00:19:11: And then this can get reactivated, the virus can get reactivated, for example if we have a lot of stress and then the virus replication starts again and then you get a full-blown infection.

00:19:25: Retroviruses are similar, they have a similar mechanism but it's a little bit more complicated.

00:19:30: So they are RNA viruses And when they enter a cell, they transform their genome into DNA and then insert it directly into our genome.

00:19:40: So that information, that viral genome, really becomes part of our genome.

00:19:45: And this, of course, can have terrible consequences, as we see with HIV, which is one of the viruses that can do that.

00:19:52: Some of these persistent or chronic infections can also lead to cancer.

00:19:55: The human papilloma virus, or HPV, is such an example where a virus infection chronic virus infection, persistent virus infection in the end leads to the development of cancer.

00:20:08: Another example is the hepatitis B virus that can also basically cause chronic infections that then lead to liver cancer.

00:20:15: So just because a virus doesn't abuse the cell right away as virus factory doesn't mean that it's harmless.

00:20:22: And there can be negative consequences in the long run.

00:20:26: But for acute virus infections, the virus enters It takes control and then, as I explained earlier, forces the cell to make more virus, with the consequence that the cell dies in the end usually.

00:20:40: Either because all the resources are used up or because the cell sensed the virus and committed suicide.

00:20:47: And there's a number of ways for cells to do that.

00:20:51: They have innate immune sensors that are able to specifically detect bits and pieces of viruses.

00:20:58: And of course such a cellular suicide stops viral reproduction.

00:21:02: If the cell is dead, the cell can make more virus.

00:21:06: And that in a way is helpful if the cell recognizes early enough that it is infected.

00:21:12: And then of course there's another possibility and that is that an immune cell recognizes that the cell is infected and just kills it off.

00:21:20: And this mechanism of course also helps to slow down and resolve infections.

00:21:25: So just to take a step back, Cells are infected, the virus replicates and spreads in the body and then in the end the host either dies from the infection or the host recovers and that's actually much more likely in most cases.

00:21:41: But that means either way that this would be a dead end for the virus because if the host is dead that also means the virus can't replicate anymore.

00:21:50: or if the host recovers that means the virus infection is also over.

00:21:54: And in order to survive, the virus has to infect the next host, the next person, right?

00:22:00: It has to spread.

00:22:02: And there are many ways to achieve that.

00:22:03: There are many infection and transmission routes that exist that viruses use.

00:22:08: And it's very important to point out these differences because the various transmission routes or infection routes make some viruses much more dangerous than others, especially in terms of pandemics.

00:22:21: Some viruses can easily be stopped from spreading while for others it can be super difficult and that often depends on the transmission routes.

00:22:32: So viruses that infect the airways, the respiratory system are often transmitted by respiratory droplets and aerosols.

00:22:41: And those are hard to stop.

00:22:43: Just to specify this a little bit, droplets means larger liquid particles that do not stay in the air for a long time.

00:22:52: while aerosols are very tiny liquid particles that can stay in the air for a very long time.

00:22:59: Droplets are typically produced when people sneeze or they cough or they talk very loudly or they sing, but aerosols can be produced by just breathing.

00:23:09: And if there are viruses in these droplets or aerosols and these droplets or aerosols are inhaled by someone else or they simply land on somebody's mucosal surfaces, then the person may get infected.

00:23:23: And this spread via the respiratory tract is really hard to stop.

00:23:27: That can only be done with masks, like N- ninety-five masks for example.

00:23:32: And especially when a virus spreads via these tiny aerosols, it's very hard to stop.

00:23:37: With droplets, it's a little bit easier.

00:23:39: And so this is transmission route, an infection route that's problematic in terms of new outbreaks and pandemics.

00:23:47: It is also possible to get infected via objects.

00:23:50: For example, if somebody is infected with a certain virus and touches a cell phone, the virus then lands on the cell phone, then somebody else touches their cell phone.

00:24:00: Now that person has the virus on his or her hands and then touches the eyes or the mouth or the face somewhere, then the virus can infect that person too.

00:24:10: And we call that transmission via fomites.

00:24:13: In this case, fomites basically just mean objects or transmission via objects.

00:24:19: Then there's viruses that are transmitted via direct contact between two people or via bodily fluids.

00:24:25: There can be transmission via vectors.

00:24:28: What is meant by that is viruses that are transmitted via mosquitoes or ticks that bite.

00:24:34: individuals and transmit viruses like that.

00:24:37: We have also in the past seen transmission of viruses via blood products and donated blood.

00:24:43: So there are really many different ways of how viruses can be transmitted and it's usually specific to that virus.

00:24:51: But especially if you talk about viruses with pandemic potential, we are mostly concerned about viruses that spread via the respiratory tract because they are so hard to stop.

00:25:01: We often hear about outbreaks with super deadly viruses in the media, like Ebola, for example, or Marburg virus.

00:25:10: And people are really afraid of these viruses and worry that there would be a pandemic with Ebola virus or Marburg virus.

00:25:18: Again, because these viruses are so deadly, they have a very high fertility rate.

00:25:23: Basically, they kill most people that are infected with them.

00:25:26: They typically spread via direct contact and via bodily fluids and it's very unlikely that a virus like Ebola will ever cause a pandemic because in the end it's very easy to stop just by using barriers like gloves and by using basic hygiene.

00:25:43: And so maybe we shouldn't worry too much about these super deadly viruses except of course in the case where we had close contact with the virus or with somebody who was infected with the virus.

00:25:55: On the other side we have something like SARS-CoV-II which actually can be transmitted via aerosols and that is a virus that is really really hard to stop.

00:26:06: So this is an example of a virus that is a respiratory virus that is transmitted via this tiny aerosols and where you really need to use specific very good masks like N- ninety-five masks to stop the spread of the virus.

00:26:23: So those are viruses that I would be really concerned about when it comes to pandemics.

00:26:29: So these transmission routes are really important and allow us to assess how easily an outbreak can be stopped to a certain degree.

00:26:36: There are a few more epidemiological terms that I would like to explain.

00:26:42: One of these terms is the R-naught or basic reproductive number.

00:26:46: This number tells us to how many people an infected person will pass on the infection.

00:26:53: It basically tells us how fast the virus will spread and how easy an outbreak can be stopped.

00:26:59: One virus that is extremely infectious, just to give you an example here, is the measles virus.

00:27:06: The measles virus has an R not of eleven to eighteen, so that means on average one measles infected person infects eleven to eighteen other people if they are not vaccinated, if they don't have immunity.

00:27:20: And that's a large number of people and that's why measles is actually so hard to stop.

00:27:26: And that's why we have such a big issue right now with measles outbreaks.

00:27:30: Influencer, so seasonal influencer on the other side has a relatively low R naught.

00:27:36: It's only about one point five.

00:27:39: So reproductive number of about one point five, which means that it's much easier to stop.

00:27:44: And that also explains why there was so little influenza circulation during the covid-nineteen pandemic because of all the travel restrictions and the masking and the social distancing.

00:27:54: And that had really a huge impact on influenza transmission.

00:27:58: And there are not a reproductive number of influenza is is lower, much lower than that for SARS-CoV-II.

00:28:06: So it was harder to stop SARS-CoV-II, but.

00:28:09: As I said, there was a huge impact on influenza transmission during the pandemic.

00:28:14: So the R-NOT is also pretty important and provides an idea of how easily a virus can be stopped.

00:28:20: Also, if the R-NOT is below one, the virus will disappear by itself and an outbreak will just end by itself because if one infected person infects less than one person, there are fewer and fewer infections over time and the virus will just disappear.

00:28:37: Then there are the terms case fidelity rate and infection fidelity rate.

00:28:42: So case fidelity rate is the number of deaths per number of detected infections.

00:28:48: So if I have hundred infected people and fifty of them die, I have a case fidelity rate of fifty percent.

00:28:55: And that's also super important number, especially when there is an outbreak with a new virus, because it tells us how severe the infections are and how big the problem is.

00:29:06: The issue is the case fidelity rate is that it's based on detected cases.

00:29:12: But many viruses also cause asymptomatic infections or milder infections that might not be diagnosed because maybe not enough PCRs are available, not enough tests are available.

00:29:23: And this was the case in the beginning with SARS-CoV-II, for example.

00:29:27: And so it might be hard to figure out the actual number of infections.

00:29:32: However, this can be done via serology studies.

00:29:36: to basically look at how many people developed antibodies to the virus.

00:29:42: and that also captures asymptomatic cases or cases that were not diagnosed.

00:29:47: and if you do that with that data we can calculate what we call the infection fidelity rate and that's the number of deaths in relation to the true number of infections.

00:30:00: and for many viruses because there is asymptomatic infections and mild undetected infections, the infection fidelity rate is often much lower than the case fidelity rate.

00:30:11: Another important term is the incubation time.

00:30:14: That's the time from between the exposure when the actual infection starts to the time when the first symptoms occur.

00:30:22: And this time interval can be pretty long.

00:30:26: So for rabies, for example, this can take weeks or a month.

00:30:31: And with other viruses, this can be pretty short.

00:30:34: For example, for influenza viruses, the incubation time is about twenty-four to forty-eight hours.

00:30:41: So, in one case, weeks to month, and in another case, just a few hours, right?

00:30:48: And when we think about the incubation time, we also have to keep in mind that in some cases, people can already pass on the virus during that incubation time.

00:31:00: that's for example the case with SARS coronavirus too.

00:31:03: And that means that people can spread the virus already before they even know that they are sick.

00:31:09: And that makes it much easier for the virus to spread, right?

00:31:12: If you can only spread the virus and pass on the virus once you're sick, it's much easier to stop because once you're sick, you know that you're sick, you might self isolate and then you might not infect anybody, right?

00:31:27: But if you don't know that you're sick, then that is much harder to do.

00:31:32: And unfortunately, as I said, that's the case with SARS coronavirus too.

00:31:35: There are a few more terms that I used often and that I would like to explain.

00:31:41: One term is emerging viruses.

00:31:44: What does that mean?

00:31:45: That means viruses that did not cause issues in the past, but that are starting to cause issues.

00:31:52: and start to cause trouble.

00:31:54: Then we also have the term of reemerging viruses.

00:31:57: Those are viruses that we had under control in the past, but we are now losing control over them again.

00:32:03: And measles virus is one such example.

00:32:06: If you go back a little bit in history, in North America and in Europe, they were not really an issue, but now we have relatively large outbreaks again.

00:32:16: Another important term is zoonotic infection and zoonotic viruses.

00:32:20: What is meant here are viruses that usually circulate in animals but then jump over the species barrier and start to infect humans.

00:32:29: So basically a virus is transmitted from an animal to a human in this case.

00:32:34: And that's important because this is how almost all of the pandemic started.

00:32:38: Then there's the term epidemic which means a large outbreak that is restricted to a certain population or to a certain area.

00:32:47: And then we have the term pandemic, which means the infection of a large number of people across a large geographic area, often globally.

00:32:57: It doesn't have to be globally, but usually a very large geographical area is involved, often more than one continent.

00:33:06: So those are a few of the important definitions that people should have heard of.

00:33:11: Now I also wanted to say a little bit about outbreaks and pandemics.

00:33:15: The reality is outbreaks with new viruses happen on a regular basis.

00:33:20: If you look back at the last thirty years we had countless outbreaks which also got media attention with outbreaks in the emergence of the handra virus, Nipah virus, different avian influenza virus strains, SARS coronavirus one in two thousand three, Ebola showed up on a regular basis, we had a Zika virus outbreak, we had yellow fever, we had hunter viruses, we had Lassa fever, M-Box more recently, also Bolio came back even in New York City a few years ago, Mabuk virus and so on and so forth.

00:33:55: These things happen constantly basically, but most of these outbreaks actually don't have larger consequences.

00:34:03: Of course, people who are infected in these outbreaks, for them that's terrible and of course also people who are close to the outbreak area can be affected, but most of these outbreaks do not lead to pandemics.

00:34:16: They are not a problem for the global population.

00:34:18: But the two pandemics that occurred in the last thirty years were the H-one, N-one influenza pandemic in two thousand nine.

00:34:25: So there was swine flu and the covid-nineteen pandemic of two thousand nineteen and two thousand twenty.

00:34:31: But compared to the rate of outbreaks, that's actually not a lot of pandemics, right?

00:34:36: Because there's a lot of these outbreaks and most of them don't seem to have larger consequences.

00:34:41: If people are interested in all of these outbreaks, you can register for a mail server that's called bromad mail.

00:34:48: I'll provide the link here in the description for the podcast and if you sign up there you can get frequent updates on what actually happens in real time with reports from doctors and scientists around the globe about outbreaks and specifically zoonotic infections.

00:35:07: You may get nightmares from reading these emails but it also shows that most of these outbreaks are inconsequential for the global population.

00:35:16: If you look back at Last approximately hundred years we had six pandemics, which sounds little when considering these numerous outbreaks that we see all the time.

00:35:29: We had an H-one and one influenza pandemic in nineteen eighteen, that was also called Spanish flu, and that had a huge impact.

00:35:37: It killed between twenty to a hundred million people, depending on the studies, the estimates.

00:35:44: We had another influenza pandemic in nineteen fifty seven.

00:35:47: with the H-II and II subtype with about two to three million deaths, then another influenza pandemic in nineteen sixty-eight, in this case with the H-III and II subtype, and also about two to three million deaths.

00:36:01: Then in nineteen eighty-one, nineteen eighty-two, the HIV pandemic started, and that's still ongoing, with about forty-two million deaths so far.

00:36:11: In two thousand nine, we had another influenza pandemic, which was caused by the H-one n-one subtype and swine flu strain and that costs about twenty fifty thousand to three hundred thousand deaths.

00:36:25: and then of course we had the two thousand nineteen two thousand twenty covid-nineteen pandemic that was caused by SARS coronavirus two and here the official death count is around seven million but estimates based on excess mortality point to around thirty million deaths so that's not a small number.

00:36:43: Where are these viruses coming from that cause these pandemics?

00:36:47: And here we have to come back to these zoonotic infections.

00:36:50: In principle, all these viruses come from animals and started to infect humans at some point.

00:36:57: And this was the case for all the foreign influenza pandemics in the last approximately hundred years.

00:37:04: This was the case for HIV and it was very likely also the case for SARS coronavirus too in COVID-IX.

00:37:11: Of course we already have a lot of viruses that circulate in humans and that cause a lot of issues like measles virus for example or different herpes viruses or rhino viruses and so on and so forth.

00:37:25: Again many of these actually cause huge issues.

00:37:28: but the problem is if a new virus jumps into humans from animals there's a big difference there.

00:37:35: And the difference is that there is no immunity against this new virus in the human population because the virus hasn't circulated in humans before.

00:37:43: And so if a new virus jumps, there is no immunity and that allows the virus to really burn through the human population and that's basically causing a pandemic.

00:37:53: And this is in contrast to viruses that already circulate where a large proportion of the human population actually has immunity to a certain extent.

00:38:04: And there are also often vaccines available against these viruses that already circulate in humans that can provide protection.

00:38:13: So these zoonotic infections are really the big problem in terms of pandemics.

00:38:18: So if you look at the number of these reported outbreaks with zoonotic viruses, we see that they are increasing and there are several different reasons for that.

00:38:28: So the first reason is a relatively trivial one.

00:38:31: Of course, we're now much better in detecting and diagnosing new infections.

00:38:37: If you go back fifty or seventy years and there was an infection with a new virus, let's say in rural Nigeria and the outbreak didn't really spread, there may have been some reports about this and this might have been called a tropical fever and probably there was not much of an investigation and usually nobody found out what actually caused it.

00:39:00: it wouldn't be reported in a way that this is a new outbreak with a new virus.

00:39:05: Nowadays it's much easier to identify these things and the media would report it and this is likely one of the reasons why we hear more about these outbreaks.

00:39:15: On the other side there's likely also a real increase in zoonotic infections and outbreaks.

00:39:22: There are more and more people on this planet and with an increase in the population size the chances of somebody getting infected with a zoonotic virus increases as well.

00:39:33: Also, more people means we need more livestock to produce more food.

00:39:38: And that means that the interface between humans and animals increases.

00:39:42: And that leads to a higher risk as well.

00:39:44: So more people and more livestock, more animals.

00:39:48: means that there's a bigger interface and the bigger the interface between humans and animals is, the higher is the chance of a virus jumping and causing an outbreak.

00:39:57: Another point is risk-through climate change.

00:40:00: This mostly has to do with vectors, so mosquitoes and ticks that spread disease and spread virus infections.

00:40:08: Many of them need warmer climate to survive and because of climate change some species like for example the Asian tiger mosquito, increase their range into temperate climates.

00:40:20: That happens in Europe, that happens in North America, and they bring viruses with them.

00:40:24: Viruses like dengue or chikungunya virus, which previously have not been an issue in these regions.

00:40:31: Another example here is the hyaloma tick.

00:40:34: That's a tick species that typically is found in warmer climates, but now spreads north in Eurasia.

00:40:42: and that tick can carry the creamy and congo hemorrhagic fever virus.

00:40:48: and basically climate change is expanding the range of this tick and with the tick it's also expanding the range of the virus.

00:40:56: Climate change can of course also lead to changes in human behavior and maybe microbes can survive better in certain areas when the climate changes.

00:41:06: And it's not completely clear yet which other surprises climate change will bring in terms of infectious diseases.

00:41:13: That's something that really needs to be monitored and I hope we are not in for too many bad surprises there.

00:41:19: Another problematic point is destruction of natural habitats.

00:41:23: Just as an example, if you have a... potentially problematic virus that only exists deep in the rainforest in the Amazon region where nobody ever comes in contact with the virus is actually not an issue right because if nobody gets infected there is no problem.

00:41:40: but if the forest is cut down to produce farmland and people settle there then all of a sudden there might be contact between humans and the virus and that could of course create an issue.

00:41:53: The final problem or the final issue that might lead to more of these infections or at least to spread of these infections is the interconnectivity of the world, of the modern world.

00:42:05: If you go back a hundred or a hundred fifty years, it wasn't so easy for a virus to cross the Atlantic, for example, right?

00:42:13: That would have been by ship, that took a long time, a week or longer, and with some luck the virus would have burned itself out on that ship.

00:42:22: before the ship actually arrived the other side of the Atlantic.

00:42:25: Today that's a very different story.

00:42:28: With air travel you can get from any place A to any place B on this planet within twenty four hours.

00:42:35: So just as an example you can get infected in Mongolia with a new virus and be in New York City before you even get sick and that makes it also much harder to stop these outbreaks from going global and becoming a pandemic.

00:42:49: So this Connectivity combined with an increased risk of zoonotic infections of course increases the risk for future pandemics.

00:42:59: I believe we need to be prepared for that and we will certainly talk more in future episodes about pandemic preparedness.

00:43:07: We will also talk about different types of viruses, we'll talk about specific risks, but I think that Was it for today with an introduction about virology, epidemiology, outbreaks and pandemics?

00:43:21: As mentioned, we'll try to get one episode online every week in the future, usually shorter than the one today, maybe around fifteen minutes.

00:43:30: But we may also have some longer ones about immunity and vaccines, for example.

00:43:37: If you have any comments or questions or suggestions, please write an email to virological.

00:43:43: at podcastwerkstatt.com.

00:43:47: Just to explain the name a little bit, I know this is a little bit hard to understand, but a podcastwerkstatt basically is the producing company that does this with me.

00:43:56: And Werkstatt translates into workshop in German.

00:44:01: And so these are the guys who helped me to produce the podcast and that's the email address.

00:44:07: I'll also put the email address into the notes so that it's easier to understand.

00:44:12: Virological at podcastwerkstatt.com.

00:44:15: We'll likely also have Q&A episodes every now and then.

00:44:20: So if people send in questions, you can actually address them, talk about the questions.

00:44:25: And I will also try to add sources and links to the literature for each episode in the comments section.

00:44:32: So thanks for listening in and until next week.

00:45:12: Bye!