#34 – Junin Virus: a 30 Percent Fatality Rate, but There's a Vaccine

00:00:05: Typically, for about seventy to seventy-five percent of individuals they start to recover in the second week.

00:00:12: That's when adaptive immunity kicks into antibodies and T cells.

00:00:16: but unfortunately twenty or thirty percent die from infection.

00:00:33: Birological with Florian Kramer.

00:00:46: All right!

00:00:47: Welcome this episode of Virologicle.

00:00:49: This was recorded on September twenty seventh of twenty twenty six Western Syria and Austria.

00:00:58: So today we're going to South America, where I'm gonna talk about a virus that's called Hunin Virus And it is the cause of Argentine hemorrhagic fever.

00:01:07: so Hunin virus isn't an arena virus.

00:01:10: It related to LASA virus for example.

00:01:13: but Hunin viruses are new world arena virus while LASa virus is old-world arena virus.

00:01:21: They call it Arena Viruses because how they look under electron microscope Arena is Latin and means sand.

00:01:29: And these virus particles back ribosomes from the host cell, so you can find ribosome in the virions... ...and when we look at that under the electron microscope it looks like little sand corns!

00:01:44: That's where their name comes from.

00:01:46: Honinvirus and all arena viruses are classified as negative single stranded RNA viruses.

00:01:55: But they do have ampi-sense coding for proteins.

00:01:59: So, there are two segments to genomic segments.

00:02:03: one is called S and the other is called L And ambi-Sense Coding just means that One open reading frame is encoded by basically the minus sense and another one plus sense orientation.

00:02:21: The s segment stands for small encodes for a nucleoprotein and glycoproteins.

00:02:29: In this case, it's called glycoprotin complex that is basically the spike protein.

00:02:35: but its got complex because this glycopprotein made as one protein But then it's cleaved And consists of glycopotin-one, glycopoten-two... ...and in this case The signal peptide stays with the complex.

00:02:52: That's odd.

00:02:53: That's typically not what happens with signal peptides of a transmembrane proteins.

00:02:58: Usually they are just removed, and so this is an example where the signal peptide actually stays with the protein.

00:03:07: And then we have the L segment or large segment that encodes for the polymerase and matrix-protein which is called Z. The particles are fifty to three hundred nanometers in diameter And basically on the inside you have your genome, there are RNA segments that are covered by nucleoprotein and then you have an associated polymerase for these segments.

00:03:33: As I said, ribosomes are sometimes found in this particles.

00:03:38: Then we have a matrix protein, then a lipid envelope... ...and in this lipid envelopes we have the glycoproteins, the spike protein Maybe also interesting.

00:03:49: The glycoprotein binds to human-transferrin receptor one, which is a receptor that's super important for iron transport in humans or I mean in mammals.

00:04:01: But it probably also binds other receptors.

00:04:04: we have seen so specifically binds to the human version.

00:04:08: but in lab mice the virus can replicate little bit even though It doesn't bind to their transferrin receptors and must use different receptor.

00:04:19: So, human transfer and receptor one is probably important specifically in infection of humans as a receptor but there might be others as well.

00:04:29: The disease was first described in nineteen fifty three in La Bamba region or province of Argentina And the virus was then isolated in nineteen-fifty eight.

00:04:42: It's named after Hunin and Hunin is a city in the Buenos Aires province with a population of about eighty-five thousand people.

00:04:51: So not very big, but that's where the virus can be found as well... Not necessarily in cities and surrounding areas.

00:05:00: The virus is carried by rodents.

00:05:02: The main natural host is Calomis musculinus or the dryland wasper mouse That cute little rodent that is prevalent in areas in Argentina.

00:05:15: but the virus can also be carried by a codon azarai, that's a grass mouse and also by oligo rizomis flavescens.

00:05:27: That is the yellow bigny rice red And thats interesting because that's the rodent it carries on this virus.

00:05:36: But yeah as I said the main host is the dryland vesper mouse.

00:05:42: In these mice The virus often doesn't cause disease and it's based on from mouth partially through grooming, through fighting.

00:05:51: And then there is also transmission from mums to the offspring.

00:05:55: so you have a reservoir of virus in these mouse populations.

00:05:59: What important dimension.

00:06:01: this mice are not domestic rodents So they don't go necessarily into houses.

00:06:05: They live in fields.

00:06:10: that explains why typically more males are infected with this virus than females.

00:06:17: That's because males are more likely to work in the fields and most infections actually happen in the countryside, in rural areas which also makes sense because that is where agriculture happens.

00:06:28: Initially the virus was only found in a small geographic area in these mice but it has expanded.

00:06:35: so initially there were La Bampa district then the Buenos Aires district, infections can also be found in the Cordova District and sometimes in the Santa Fe District in Argentina.

00:06:48: So there's an expansion of the geographic area.

00:06:52: Typically they are three hundred to five-hundred cases per year but what I've read last few years were fewer or even lower than twenty which I guess is good, but the geographic expansion is problematic.

00:07:10: How do people get infected?

00:07:12: This virus is transmitted from mice to humans so typically there's no human-to-human transmission.

00:07:18: it's really mouse to a human and the mice excrete the virus via urine and feces And...so People can get infected when they consume contaminated food or water Or if they inhale dust that contains urine or feces, dried urine or dried feces with the virus.

00:07:39: So similar to what we see with Hunter viruses for example.

00:07:43: and then there can also be infections when people have open wounds or skin lacerations and they come in contact with their feces.

00:07:53: And initially this virus infects macrophages.

00:07:57: They carry them into lymph nodes where it starts to replicate.

00:08:02: The incubation time is six to fourteen days and the disease usually comes in three phases.

00:08:10: There's a prodromal phase, I'll explain how these phases look like.

00:08:15: then there's a neurological and hemorrhagic phase And then there are convalescent phase.

00:08:21: Alternatively In about twenty-to thirty percent of infected individuals ,there no convalecent phase because they die from infection.

00:08:31: case fidelity rate is twenty to thirty percent.

00:08:35: And death usually occurs seven to twelve days after symptom onset, so it's a very severe disease.

00:08:42: First you have this prodromal phase that when the disease starts This looks like influenza People get fever, malaise they don't feel well chills headache muscle aches and then these moves on or progresses this neurological and hemorrhagic phase.

00:09:03: And there we can have symptoms like photophobia, retroorbital pain, dizziness, seizures even coma... ...and then there's GI tract involvement with nausea, vomiting.. ..and either constipation or diarrhea has been reported….

00:09:21: …and you also see these haemorrhage symptoms in some cases on the one side Betechia, which are red or purple spots of skin normal coastal surfaces.

00:09:31: They indicate bleeding in these coastal surfaces under their skin and then there can be blood in urine or vomit.

00:09:40: And hemorrhagic symptoms are caused by inhibition of platelet aggregation by the virus and thrombocytopenia.

00:09:48: Typically for about seventy to seventy-five percent they start to recover in the second week.

00:09:56: That's when the adaptive immunity kicks in, antibodies and D-cells.

00:10:01: but unfortunately twenty to thirty percent die of infection.

00:10:07: There is an interesting symptom in the convalescent phase so people are already getting better.

00:10:11: there can be temporary hair loss which is a very interesting symptom.

00:10:16: The good thing is that there actually countermeasures.

00:10:20: Vaccines against Hunin virus have been developed relatively early.

00:10:24: There's one vaccine that is used in Argentina right now, it's called Candid One.

00:10:29: It's a classical life attenuated vaccine and was actually developed by the US Army Medical Research Institute for Infectious Diseases U.S.

00:10:38: M-Raid in Fort Detrick.

00:10:41: And what they did... This is typical of classic life attenerated vaccines.

00:10:46: They just started to passage the virus into different animals cells.

00:10:53: The passage did initially two times through guinea pigs, then forty-four times through mouse brains and then nineteen time thru cells from resus macaques.

00:11:05: And there was a clonal selection afterwards which means they purified single infectious particles.

00:11:12: you can do that via plug assay by picking plugs or doing what we call limiting dilution And they ended up with a virus that was not pathogenic anymore, but still able to replicate and induce good immune responses.

00:11:29: As I said this vaccine is used in Argentina and it has a ninety-five percent efficacy so its very good vaccine.

00:11:36: This really helped bring down case numbers.

00:11:39: If people are already infected They can be treated.

00:11:42: There's one treatment out there That can be used and thats plasma preparations from people who survive the infection.

00:11:50: So these people then have neutralizing antibody in their plasma and their serum, that can be used if it's given to infected individuals within eight days of symptom onset.

00:12:03: this cuts down a case fatality rate from twenty-to thirty percent to one or two percent.

00:12:10: The problem is that this plasma treatment actually comes with its own side effects.

00:12:17: about eight to ten percent who get this plasma treatment have late neurological symptoms.

00:12:25: So basically the virus initially is suppressed, but some of it seems to make it through...to brain and I think to cerebellum mostly And It Seems To cause Some inflammation there and This can lead to these late neurological Symptoms which also include fever for example a number usually relatively mild neurological symptoms.

00:12:50: And from what I've read, this is often self-limiting so it's not super serious but of course having virus in your brain isn't great.

00:12:57: We basically have pretty good countermeasures for Honin including a vaccine and this plasma treatment.

00:13:05: Ofcourse.

00:13:06: It would be better to have monoclonal antibodies as treatments.

00:13:10: Monoclonals antibodies are much more defined products than Plasma people who survived the infection.

00:13:18: And I'm bringing this up because we were just about to publish a paper where he made such antibodies and showed that they can protect, at least in animal models very nicely against infection.

00:13:31: The last thing to mention here is that Hunin is not only New World arena virus.

00:13:37: that's around.

00:13:38: there are plenty of them In Central and South America.

00:13:42: There even some North America.

00:13:46: The viruses worth mentioning here are guanarito virus in Venezuela, sabia virus in Brazil and achupovirus in Bolivia.

00:13:55: And these viruses can cause relatively similar disease also relatively severe diseases... ...and for them there's no vaccine or there're no vaccines.. ..and they have no treatment options so They seem to be lower in prevalence.

00:14:09: as far I know that might the reason why their not counter measures but at least four who mean we have the countermeasures.

00:14:17: So that's it for today, as always if you have any comments concerns questions please write an email to Virological at podcastworks.com and If You like this podcast feel free To support It on Steady.

00:14:31: Thanks For Listening And Until Next Week Bye!

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