#20 – Alongshan Virus: a New Tick-Borne Virus in Europe

00:00:06: And so out of these approximately thousand, four hundred samples they found two people who had antibiotics against both of the proteins and relatively high titers.

00:00:14: That really shows that also in Europe this long shunt virus can infect humans.

00:00:33: Virological with Florian Kramer.

00:00:46: Hello!

00:00:47: Welcome to today's episode of ViroLogical.

00:00:51: This was recorded on June twenty-second of twenty-twenty six in New York And today we're going to talk about a very interesting virus that's called Alangxian virus.

00:01:02: This is viruses, it has a little bit like a flavivirus and its related to flaviviruses but its special!

00:01:10: It belongs to the Ginos Jingmen virus which... The Ginos itself are part of the family of Flaviviridae.

00:01:18: so thats where the orthoflavivirisus, the real flavivirsus are also located.

00:01:24: But these Qingmen viruses are very weird in a way that they have segmented genome.

00:01:32: So typically, flaviviruses like dengue virus for example... ...they have positive polarized single-stranded RNA genome.

00:01:43: but this Qingmen virus actually has genomic segments.

00:01:47: so regular flavivirus just had one genomic segment and one strand.

00:01:53: Qingmen viruses have four, some of them even have five.

00:01:58: And a Longshan virus is one of these viruses.

00:02:01: so this Qingman viruses in general were discovered.

00:02:04: around two thousand fourteen at least that's when they were published for the first time.

00:02:09: there are found in samples from ticks from two thousand ten I believe and it's now known to circulate intakes and mosquitoes and whenever discover.

00:02:18: this was very interesting thing.

00:02:20: very curious because they had this segmented structure.

00:02:24: And the point is that two of these segments, S-one and S-three segments encode for proteins very similar to proteins that real flaviviruses have.

00:02:38: The S one segment encodes for NS five which is polymerase which is also a protein that's found in real flaviviruses, but then the S-II segment potentially codes for a spike protein or two spike proteins depending on the virus.

00:03:00: But they don't have any proteins in flavivirus that are related so we do not know how these envelope or spike proteins of the Jinmen viruses actually look like.

00:03:13: And the fourth segment also codes for viral proteins that have not really known functions.

00:03:19: They're called virus-proteins two and virus protein three, so in general parts of these viruses look similar as flaviviruses... ...and other part of this viruses looks different or completely different?

00:03:35: Then there's this segmented nature of the genome which is also weird because we don't see it in regular flavivirus.

00:03:42: It's almost like a flavivirus and an influenza virus have a child.

00:03:47: Influenza viruses, they've had genomic segments.

00:03:49: so in a way it looks like a hybrid but that is not what this is from the molecular perspective completely different.

00:03:58: anyways these viruses are typically eighty to hundred nanometers in diameter And when you look at electron microscopy pictures of elongation virus It actually doesn't look like a flavivirus, right?

00:04:10: Flaviviruses are smaller.

00:04:12: Usually they're forty to sixty nanometers in diameter and if you have very regular structure that looks like a volleyball.

00:04:19: there really pretty viruses.

00:04:21: That's not the case for these jingmen viruses And certainly no for long-shan virus.

00:04:26: it is little bit more biomorphic so its not as regular structure.

00:04:32: So their definitely different.

00:04:36: Again, these viruses were discovered.

00:04:38: The whole group of twin-man viruses was kind of a curious thing that potentially circulates in.

00:04:45: this virus is potentially circulating insects.

00:04:48: nobody really thought they could be problematic for humans.

00:04:52: and if you go back there's only one sequence associated with the human and it was found in patients in Kosovo or Europe and that patient had a cream congo hemorrhagic fever virus infection.

00:05:07: Cream congo haemorrhage fever virus is a boonier virus, which also transmitted by ticks can cause very severe infections.

00:05:15: when material from the patient was sequenced they found a ching men's virus there but this virus wasn't causing disease.

00:05:24: it probably decked along with these cream congos hemorrhagic fever virus and then maybe replicated a little bit in that tumor.

00:05:34: But other than that they were only found in insects, I think ticks are technically not the insect but this changed a little within in two thousand nineteen.

00:05:45: In twenty nineteen really nice new angel of medicine paper came out i remember we had it for John Clappier at Monsignor And that described the discovery.

00:05:58: And this started with one index patient, I think a farmer.

00:06:03: A forty-two year old female farmer from down in China and the town is called Alangshan Chen.

00:06:13: That person was admitted to hospital in two thousand seventeen With fever headache.

00:06:18: on history of tick bites The presentation was similar like DBB Just put it into place for geography.

00:06:28: Alangshan Chen is in the northern part of Inner Mongolia.

00:06:31: Inner Mongolia is one province of China, and so this is a town that's relatively close to the Russian border already not very close but at the very north end part of inner Mongolia Very rural part yeah.

00:06:46: So this person was admitted to their hospital And the researchers there took samples from that person including serum.

00:06:53: They tried to culture virus.

00:06:57: the person was probably tested for all kinds of virus infections, but none of that was positive.

00:07:02: So they tried to culture whatever was causing this infection and for that often viral cells are used.

00:07:09: so as you remember You can't just put viruses into a sugar solution or some kind of broth.

00:07:15: They cannot grow on their own .They need cells to replicate right?

00:07:19: They need to infect actively infected cells.

00:07:22: And so what virologists often use for these viral cultures is vero cells.

00:07:27: Vero cells are derived from African green monkeys, it's a cell line that you can indefinitely grow in the lab and just cultured into liquid media... ...and they have damaged innate immune response.

00:07:40: So they cannot fight viruses off very well.

00:07:43: That why the cell line is popular with virologist because their cells are very susceptible to virus infections Because they cant fight them of.

00:07:51: And so one delt little sign that the virus is growing in these cultures, it's that the cells are dying.

00:07:58: So exactly what this researchers saw when they inoculated these cell cultures with samples from that person... They saw that the sales were dying and there was an indication of the virus being there.

00:08:11: they performed electron microscopy.

00:08:13: They could see particles, various particles that didn't look like flaviviruses not like DBV which is something that they suspected initially but it looked bigger as I described earlier.

00:08:25: and then they tried to sequence this virus and there's two ways to do sequencing.

00:08:31: If you know what your looking for, it can do that very targeted.

00:08:35: You can perform a PCR and then sequence whatever you amplified in the PCR In terms of genetic material.

00:08:42: That is how sequencing is traditionally done But theres new methods that are basically called meta-genomics where they can do the sequence independent.

00:08:52: So if just look at all these sequences And so they did that and found four segments of a new Qingmen virus.

00:09:02: Because the patient was from a Long Shan Gen, They called this virus A Long Shan Virus.

00:09:08: Now they had a sequence... ...and saw it as an infection caused by this Long Shan virus.

00:09:19: So they wanted to go back and see if they could identify other cases approximately four hundred samples from patients in Inner Mongolia and a neighbouring province, Heilongjiang.

00:09:34: And they looked for people with similar symptoms under history of tick bites.

00:09:39: In fact we found this virus in sixty patients from Inner Mongolia... ...and twenty-four patients from Heilong Jiang.

00:09:48: When you look at what these people were doing Many of them were farmers, some are forestry workers and that makes sense if you think this virus was transmitted by ticks because those people would be exposed to ticks quite a bit.

00:10:04: They also managed to isolate the virus from ticks they collected in this case exodes persucatos which is a tick species typical for that area but has relative in Europe From looking at all of that and the tick exposure, when it happens on set of symptoms in these patients they identified.

00:10:32: They calculated that incubation time for this virus infection is about three to seven days.

00:10:38: The patient typically had fever headache sometimes moderate more severe headache fatigue.

00:10:47: approximately ten percent of them have a cough which is interesting for flavivirus infection.

00:10:54: That's typically not what you see, but they reported that swollen lymph nodes was another symptom and actually all of these infections were mild.

00:11:07: approximately thirty five percent of the patients were in a coma at some point in time.

00:11:12: so this can be pretty dangerous infections it seems.

00:11:16: But in the end, all the patients that they identified recovered and survived their infection.

00:11:23: And so yeah this was in Inner Mongolia and China... ...and then in- In two thousand nineteen people started to look for these virus in ticks in Europe.. ..And one team that found it first was the team around Oliver Palatti at University of Helsinki.

00:11:44: They could identify a long shunt virus in Ticks, in Xolis Ricinos.

00:11:49: So that's the common species you have in Europe, and Finland.

00:11:55: And they could sequence the virus.

00:11:56: It was genetic a little bit different than one identified in Inner Mongolia but it certainly also a long shunt virus.

00:12:04: They looked if there were human cases or not.

00:12:09: Then over time the virus is found in Switzerland France Russia I believe in UK and in Germany, but human cases were not found.

00:12:22: In Germany people also looked... Not just in ticks for the virus directly But they also look at antibodies in different animal species.

00:12:32: So there's two ways to find these viruses.

00:12:34: One is you can do that with a PCR then identify the presence of the virus.

00:12:42: But for that, you need to sample during a window when the virus is causing the infection.

00:12:47: Where can look at antibodies?

00:12:50: When an animal or human gets infected with the virus their immune system will respond and people who get antibodies or animals would get antibodies so they could also look for these antibodies in there around for much longer.

00:13:02: So it's easier to find positives than when you do serology.

00:13:08: And so the German team did that and they found positive deer, positive goats, positive sheep and positive horses.

00:13:17: It was a small number of the samples that they looked at.

00:13:20: So their infection wasn't very prevalent but they find positive animals.

00:13:24: I think this is done in lower Saxony in Germany.

00:13:27: Then there were recent developments.

00:13:30: The reason why i'm recording these podcasts right now.

00:13:32: There's paper which just came out that was recently published by Judith Awele from the Center for Virology at the Medical University of Vienna.

00:13:45: They are really experts for tick-borne viruses and for DBV specifically, but also because they have a huge collection of ticks in the well how to work with these vectors started looking into the presence.

00:14:01: As I said this paper just came out and it's super interesting.

00:14:08: They had a number of collections, they have tics that collected in twenty-twenty four, there was field collection... ...they had ticks that has been collected between two thousand five and two thousand thirteen.... And then also looked at these human tick couples that we have.

00:14:25: These are basically matched samples where You have the tick, but then you also have samples from a human that was bitten by the tick.

00:14:34: And it's super helpful because... ...that way we can investigate if an infection is established in humans who were bitten and maybe they could look later on whether this person made antibodies or not.

00:14:48: They had these match samples from two thousand fifteen to two thousand eighteen.

00:14:53: And so via BCR, they looked specifically for a long shunt virus in about three thousand ticks from twenty-twenty four and the found prevalence of one point two percent.

00:15:05: So but one point to present after ticks were positive They also look into their historic tick sample and Sam tick samples.

00:15:13: and if it looked at about thousand eight hundred samples there and three of those samples were positive relatively low prevalence compared to other viruses that can be found in ticks.

00:15:26: In that area, Austria has a relatively high prevalence of tick-ponensive ladies virus for example which is the classical flavivirus.

00:15:35: but it was there and definitely there And they could find basically all over the country.

00:15:41: They had positives from very west of the country in the south of the county Austria's not too small was geographically spread out and also in the north of the country.

00:15:54: So it seems that its not a very common virus intakes, but is certainly present all over the place.

00:16:02: And they started to look into human samples.

00:16:05: I think there are about thousand four hundred human samples... ...and there did looks for antibodies against two virus proteins The VP-Ia which supposed be spike protein and then VP II.

00:16:18: And as I mentioned earlier, you can also when you look at antibodies detect past infections.

00:16:25: So out of these approximately thousand four hundred samples they found two people who had antibiotics against both of this proteins and relatively high titers!

00:16:34: That's kind-of cool because that really shows... ...that in Europe a long shunt virus can infect humans.

00:16:44: Now, it's not clear if these people were sick at some point and If they're sick how severe their infection was.

00:16:52: but It certainly proves that this.

00:16:54: infections can also happen in Europe.

00:16:57: now the interesting part of course is The virus was discovered in ticks in China then.

00:17:02: He was found in ticks In Europe.

00:17:05: The interesting part is how did the virus get from china to europe?

00:17:09: when did that happened right?

00:17:11: probably history evolutionary way back, it's probably not a new development.

00:17:16: What could have happened of course is that the virus over time spread with migrating birds.

00:17:22: sometimes they carry ticks around and then with these migratory birds the ticks are spreading.

00:17:28: with the ticks viruses are spread.

00:17:31: That one hypothesis there bunches.

00:17:34: other possibility is how the virus could have spread in Eurasia.

00:17:38: Again a super interesting finding, it's not very alarming right?

00:17:41: The prevalence of this virus in Europe seems to be low and also doesn't seem to have high prevalence in China.

00:17:48: there are few reported cases.

00:17:51: that don't seem too big problem but its certainly something to be aware.

00:17:56: if somebody has a tick bite then get sick.

00:18:00: A long-shined virus, specifically there's no other pathogen can be identified.

00:18:05: Like the classical ones that you would find in Eurasia after a tick bite like DBEV but also some bacterial infections.

00:18:14: Interesting virus lots of unknowns still even in terms of protein structures and protein functions certainly something interesting for virologists But probably not something regular people need to worry about.

00:18:29: That's it for today.

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