#36 – LCMV: Why Mice in Your Home Can Be a Risk

00:00:05: Humans can get infected too and here the transmission is often from mouse to humans via dried saliva, dried feces, dried urine that basically then is aerosolized and inhaled.

00:00:46: Yeah hello!

00:00:47: And welcome today's episode of Virological.

00:00:50: this was recorded on October twelfth of twenty-twenty six in New York.

00:00:57: so Today we are going to talk about the virus with a very complicated name.

00:01:03: The abbreviation is LC-MV, which stands for lymphocytic coriomanticitis virus and We talked about relative of this virus.

00:01:14: so A few weeks ago how the relatives that we talked about is Hunin virus right?

00:01:19: This dangerous virus that Causes causes Argentine hemorrhagic fever And many feel probably thought Okay, that's in Argentina.

00:01:29: That's not where I'm usually... Many of you probably thought well that is in Argentina and this isn't the place to walk around.

00:01:39: so it might be problematic but there are bad news about this virus, LCMV which is everywhere with regular house mice.

00:01:53: So we're going talk a little bit about this today lymphocytic coriomanageritis virus and I'll get to what the name means, where it comes from in a minute.

00:02:07: It's an arena virus.

00:02:08: we talked about arena viruses before like Huninvirus.

00:02:12: Arena is Latin and stands for sand.

00:02:16: And The reason why these viruses are called that?

00:02:19: because when you look at them under the electron microscope You can see this dark spots within the virion.

00:02:26: And the idea is that these dark spots, they look like sand are ribosomes.

00:02:31: They're included in the virion basically from their host cell and so as mentioned this LC-MV is related to Hunin virus but even closer related to Lhasa virus.

00:02:45: both Lhassa and LC-mv are old world arena viruses.

00:02:56: that comes as two segments.

00:02:59: And most of it is negatively polarized, but its actually an ambi-sense genome which means can be read from both sides and encodes proteins in both polarities or directions.

00:03:13: So this comes with L or large segment.

00:03:18: In the negative polarity this segment encodes a polymerase gene and then positive polarity matrix protein called Z. And then we have the S segment and that encodes N, nuclear protein.

00:03:34: And then spike-brotein in this case is called glycoprotein complex or GPC because it's made as one protein but then it's cleaved into three different parts so its glycoprotin complex.

00:03:49: When you look at the virion these virions can be quite divergent in size, they can be up to three hundred nanometers in size but usually there are around a hundred two hundred twenty nanometers.

00:03:59: They're pleomorphic.

00:04:01: what does that mean again?

00:04:03: The morphic means their kind of round but then the shape can change it into little bit more filamentous egg-shaped and so on... That's meant with pleomorphics.

00:04:15: If you look at composition of the virion inside we have the RNA genome that's covered by a nucleoprotein and is associated with the polymerase.

00:04:25: Then we have matrix protein, on the outside of the matrix protein in lipid envelope which is derived from the host cell plasma membrane.

00:04:34: And then if you look at this particle composition On the inside there are RNA genomes which are protected by the nucleoprotene.

00:04:45: There is an polymerase associated to each of the genomic segments.

00:04:49: Then we have the matrix protein and on the outside of the matrix-protein, We have the host cell derived lipid membrane.

00:04:57: And in this lipid-membrane ,we have the spike protein .And as I already mentioned, This spike protein is composed of three different parts.

00:05:07: The two main parts are GP one and GP protein One and glycoprotein Two.

00:05:15: all arena viruses happened.

00:05:17: We talked about that when we talked about Hunin as well, usually transmembrane proteins come with a signal peptide basically directs the protein into the membrane in the cell and usually this signal peptides is cleaved off then just degraded but it's relatively long.

00:05:45: that's special for arena viruses.

00:05:47: That is kind of a really special biology there, you don't find it in other cellular proteins or other viral proteins.

00:05:56: Yeah!

00:05:57: It might also be important to note that there are four genotypes of arena viruses and Genotype one two three are associated with human infections.

00:06:10: A little bit about the history and biology of the virus.

00:06:13: The virus was discovered in nineteen thirty four by Charles Armstrong when he worked at an institution that was basically the precursor of the NIH, And it's a strain that he found He isolated from cerebrospinal fluid for patient with aseptic meningitis.

00:06:33: There is lot to learn back here.

00:06:35: I'll explain That strain is still named after him, that's the Armstrong strain of LCMB.

00:06:42: Okay so I said cerebrospinal fluid.

00:06:45: what is now dead?

00:06:47: Cerebrospiral fluid is basically the fluid that protects the brain and the spinal cord And this is mostly produced by part of the brain.

00:06:59: it called corioide plexus... ...and thats next to the cerebellum in the brain.

00:07:07: That's why this virus is called lymphocytic choriumenangitis virus, because it seems to also infect the coriotelexus.

00:07:16: I've mentioned aseptic menangitis and so manangitis is an infection in inflammation of the meninges which basically one layer that protects your brain.

00:07:30: Aseptic means there are no bacteria involved And so aseptic meningitis is usually caused by viruses.

00:07:39: So basically what Charles Armstrong did, he took this cerebrospinal fluid from patient with septic meningiitis or somebody who had a meningitis because of virus infection and that's where he found the virus complicated words.

00:07:56: in nineteen thirty five.

00:07:58: The virus was also isolated from mice from house mice musculos and it turned out that the house mice are the reservoir for this virus.

00:08:10: In mice, its spreads via milk, nasal secretions, saliva, urine, feces through licking,

00:08:18: e.g.,

00:08:19: through grooming behavior but also through fighting And the mice can vertically transmit the virus.

00:08:27: Typically if all the mice get infected with LCMB they become sick.

00:08:33: The virus is vertically transmitted, meaning that the virus is transmitted from an infected mom in utero to their offspring.

00:08:43: Then these mice are born with the virus infection and they develop a chronic infection.

00:08:50: so the virus doesn't go away anymore and excrete the virus for very long time.

00:08:56: but it's not just.

00:08:56: mice can get infected, guinea pigs can get affected, hamsters can get and other wild rodents can acquire the virus as well.

00:09:07: It's also known that marmosets, these are non-human primates specific non human primates Can get infected with LCMV.

00:09:15: they happen in facilities where this animals are housed And then get contact with house mice In the Marmoset.

00:09:23: this can develop a really deadly disease.

00:09:27: Humans can get infected too.

00:09:29: Here to transmission is often from mouse to humans via dried saliva, dried feces, dried urine that basically then is aerosolized and inhaled.

00:09:40: So this is similar to what we discussed with Hunin virus but also similar towards happening with Hunter viruses in human infections.

00:09:49: But people can also get infected via contaminated foods or by bites.

00:09:55: so if you catch a mouse and you get bitten by it You can also acquire LCMV infections.

00:10:02: And then there is also vertical transmission in humans, so meaning from mother to fetus and also for mother the newborns.

00:10:10: That can be pretty problematic.

00:10:13: Then another way of transmission or how people get this virus is via organ transplantations.

00:10:22: So basically if an organ donor's infected and their organ is donated The recipient of that organ gets infection.

00:10:32: In general, most infections in humans with LC and VR are asymptomatic.

00:10:38: If people have a competent immune system meaning their immune system is well functioning it's usually not the problem.

00:10:45: There can be symptoms.

00:10:47: The incubation time is about one to two weeks.

00:10:50: And then there's first phase.

00:10:52: that is in way influencer.

00:10:53: like People get fever They don't feel eating lack of appetite they could get headache can feel bad in general.

00:11:02: Muscle aches can develop nausea, vomiting and that resolves them relatively quickly.

00:11:10: Typically during the time there is also Lycopenia occurring meaning divide blood cell count drops and tripe thrombocytopenia can occur which means platelet counts go down into the blood but again most cases asymptomatic or very mild.

00:11:28: However, there can be a second phase that can occur weeks later after this first phase.

00:11:35: After people already recovered from the first phase and their infection can develop into meningitis or encephalitis And this is of course accompanied by neurological symptoms.

00:11:50: That's more severe form of disease.

00:11:54: One of the more problematic situations is when organ transplant patients get infected, this can lead to pretty severe disease.

00:12:04: There's two ways for them to get infected via the organ that they got transplanted with.

00:12:10: so if their organ donor is infected potentially asymptomatically the virus people can get infected via contact with mice or their droppings, or by contact with pets for example pet hamsters that have LCMV.

00:12:32: In these cases the disease can be pretty severe.

00:12:37: it's almost like a hemorrhagic fever.

00:12:39: It is similar to LASA virus or Hunin virus in this case and then typically develop organ failure.

00:12:46: In this case fatality rate, the mortality rate is often above seventy percent so that's pretty problematic.

00:12:55: This is rare and doesn't happen very often but if it happens usually the prognosis for a patient.

00:13:07: Of course, this can lead to encephalitis and meningitis in pregnant women.

00:13:11: Pregnant women usually also have a slightly down-regulated immune system that makes sure the mother's body doesn't detect the fetus And it is kind of specific form of immune suppression as well so they can set them up for infections.

00:13:27: If infection happens on the first trimester This often leads to spontaneous abortions because there's vertical spread from the mother to the fetus, so the virus spreads into the fetuses and that can lead to spontaneous abortions.

00:13:42: If the infection occurs later in the second or third trimester, the virus also make it through the feters which have really problematic consequences when babies are then born.

00:13:55: this can manifest an intracranial calcification, so really calcifications of the brain Hydrocephalus, basically an accumulation of water in the brain microcephaly so meaning that the brain is relatively small much smaller than a normal brain but also do macrocephally.

00:14:16: So larger brain then usual and these things can lead to intellectual disability.

00:14:26: Of course that's highly problematic.

00:14:28: New burns can also be infected, which often leads to a very high case for deliderate as well around thirty percent and the babies that survive have lasting neurological problems too but two-thirds of the survivors has lasting neurological consequences.

00:14:49: So, in these two situations the infections are really bad.

00:14:53: In organ transplant patients and during pregnancy Unfortunately there is no treatment.

00:15:00: There's also no vaccines available against LCMV.

00:15:04: What really is saving situation Is that both of this cases are rare.

00:15:09: It's rare that organ transplant patient infected And it's also rear that pregnant women get infected.

00:15:17: This is not something that happens very often, but when it happens unfortunately can have very severe consequences.

00:15:26: So what about the prevalence of this virus in mice?

00:15:31: It's basically found globally.

00:15:33: most mouse populations have LCMV to a certain degree and these can be low or small proportion of the local population but it can also be a relatively large population.

00:15:46: I think there's, for example one study that looked into mice in Austria and Croatia and found out about twenty-five percent of the most populations on average is zero positive for the virus.

00:15:59: so basically has antibodies head contact with the virus But then some areas this can be much higher.

00:16:07: So again the viruses really circulating globally but it depends on the local population how high the prevalence of the virus is.

00:16:19: In humans, the zero-prevalence can be relatively high too.

00:16:24: in the

00:16:25: U.S.,

00:16:25: It goes up to five percent.

00:16:27: This also tells us that there's probably tons of asymptomatic infections That don't have consequences.

00:16:34: But there are hotspots globally.

00:16:36: There an island in Croatia called Vir that has a relatively high zero prevalence in the human population.

00:16:45: It's almost forty percent.

00:16:48: There is study from Pratislava and Slovakia, which also suggests very high zero-prevalence of about forty per cent.

00:16:56: Another study was done in SuperSynel in Vienna at the Zoological Garden And it found a thirteen percent zero prevalence In the personnel working there.

00:17:09: So you know There are hotspots where there seems to be more contact with infected mice and more transmission, but then other areas were the infection or zero prevalence in humans is very low.

00:17:22: I think for New York City also a study that shows actually little contacts and infections was very low antibody positivity within humans.

00:17:35: What's known as most infections occur in fall or winter in the northern hemisphere, which makes sense because that's when the mice try to move into houses and into apartments.

00:17:47: And there is also socioeconomic influence.

00:17:53: so basically lower socio-economics status correlates with higher zero prevalence.

00:17:59: That also make sense if people live in less nice houses or apartments.

00:18:07: maybe more rural areas.

00:18:09: there could be a lot more contact to rodents.

00:18:13: that includes house mice which carry this virus.

00:18:16: One story in the end, LCMV was also really important in research.

00:18:21: it's used quite a bit in research as an infection model and mice And the virus was used in studies that revealed how these cells recognize antigens.

00:18:33: The study was done by Roth Zinkernagel and Peter Doherty.

00:18:37: multiple studies of course, but they got the Nobel Prize in nineteen ninety-six for that discovery and there was basically also a Nobel prize for LCMV for this lymphocytic coriomeningitis virus.

00:18:50: So to summarize... This is a virus with very complicated name, LCMB, Lymphocytic Coriomendingitis Virus.

00:18:57: Most people don't know about it.

00:18:59: It's actually common in mice.

00:19:01: In house mice.

00:19:03: There are probably tons of asymptomatic infections in humans, but it can also lead to meningitis and encephalitis.

00:19:13: And then two cases can be highly problematic—in one case when it infects pregnant women because it can cause severe disease or severe problems in the fetus —and then in newborns.

00:19:27: On the other side, it can be very problematic for organ transplant

00:19:30: patients.".

00:19:31: All right!

00:19:33: That's all for today.

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