#26 – Travel Viruses: West Nile Fever – Now in Central Europe Too

Show notes

The final part of the summer series on vacation viruses is one you can catch without going anywhere: West Nile virus. Florian Krammer explains why this flavivirus is closely related to Japanese and St. Louis encephalitis virus, how it mysteriously showed up in New York in 1999 - most likely via mosquitoes on a container ship and spread across the entire US within a few years. It has since reached Austria too, mainly in the east (Vienna, Lower Austria, Burgenland). Birds are the real reservoir, while humans and horses are dead-end hosts. The good news: 80% of infections are symptomless. The bad news: in rare cases the virus invades the nervous system, and then the fatality rate is around 10%. A striking detail: the very CCR5 mutation that protects against HIV raises the risk of severe West Nile disease. There's no vaccine for humans, only mosquito protection helps.

West Nile virus information from the US CDC: https://www.cdc.gov/west-nile-virus/index.html West Nile virus information from the WHO: https://www.who.int/news-room/fact-sheets/detail/west-nile-virus

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Krammer laboratory information

Krammer Laboratory at the Icahn School of Medicine at Mount Sinai https://labs.icahn.mssm.edu/krammerlab/

Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness https://soap.lbg.ac.at/

Ignaz Semmelweis Institute https://semmelweisinstitute.ac.at/

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Conflict of interest statement

The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines and therapeutics, SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which name me as inventor. Mount Sinai has spun out a company, CastleVax, to commercialize NDV-based SARS-CoV-2 vaccines and I am named as co-founder and scientific advisory board member of that company.

I have previously consulted for Curevac, Merck, Gritstone, Sanofi, Seqirus, GSK and Pfizer and I am currently consulting for 3rd Rock Ventures (US) and Avimex (Mexico).

My laboratory has been collaborating in the past with Pfizer on animal models of SARS-CoV-2 and with GlaxoSmithKline and VIR on the development of influenza virus vaccines and therapeutics and we are currently collaborating with Dynavax, Inspirevax and Inimmune on development of influenza virus vaccines.

My work in the on immunity and infectious diseases in the US is supported by the National Institutes of Health, but also by FluLab and Tito’s Handmade Vodka. In the past I have also received funding from the Bill and Melinda Gates Foundation, PATH and the US Department of Defense.

My work in Austria is supported by the Ludwig Boltzmann Gesellschaft and by the Ignaz Semmelweis Institute through the Medical University of Vienna.

Show transcript

00:00:05: It's still not clear how the virus got to New York.

00:00:08: Isolates there were very closely related to isolates from Israel, I think that idea is they were larvae of mosquitoes or mosquitos themselves somehow made it on containerships in Europe and Middle East to New york where these mosquito went down to infect humans caused this outbreak.

00:00:57: Welcome to this episode of Virological.

00:01:00: This was recorded on July fifteenths, of twenty-twenty six in Vienna and we're going to continue our episodes about viruses that you can get from mosquito bites during vacation.

00:01:13: We have now talked about Toscana virus and Papadacci fever in Italy... ...we've talked about Zimpis virus in Scandinavia.. ..we've talk about Ouro Busch virus in the Americas the tropics and sub-tropics.

00:01:28: And if you hear all of that, think about this virus infections from mosquito bites on vacation then I am staying at home with very bad news for you specifically in temperate climate in North America or Europe.

00:01:49: Today we are going to talk about West Nile virus and West Nail fever.

00:01:53: West Nile virus is a flavivirus that's very closely related to St.

00:01:58: Louis Encephalitis Virus and Japanese Encephalitis Virus.

00:02:04: And yeah, it's mosquito transmitted and we'll get the specific mosquitoes in a few minutes.

00:02:11: It also more distantly related to other flaviviruses like Dengi or DBB.

00:02:16: This virus has an RNA genome with positive polarity, plus sense RNA genome that single stranded.

00:02:26: The genome is approximately eleven thousand nucleotides long so eleven thousand letters.

00:02:32: and when we look at the particle...the particles are about forty five to fifty nanometers in diameter.

00:02:41: it's very nicely shaped very symmetric.

00:02:45: this Flavivirus particles are so regular, they can be solved as a structure with different structural methods including cryoEM.

00:02:55: So you get very high resolution structures from them.

00:02:59: because there's a regular.

00:03:01: and if we look at the particle... We have RNA on the inside then we have a capsid protein ...we have a lipid membrane and we have an envelope protein that sits in this lipid membrane, then there's also a M-protein or membrane protein.

00:03:20: In addition to these what you call structural proteins because they make up the virus particle There are lots of nonstructural proteins produced by viruses when it infects cells.

00:03:32: And some of those viruses reshape the endoplasmatic reticulum.

00:03:38: The virus makes the endoplasmatic radiculum form additional varcoles, bubbles basically.

00:03:49: They're called cytopathic varcules and that's what the virus uses to replicate.

00:03:55: so it basically hides its replication machinery the virus factories from cell, immune system by reshaping the endoplasmatic reticulum and hiding the virus replication in lipid vesicles.

00:04:11: Which is very smart.

00:04:12: if you look at that in electron microscopy it looks pretty bad almost like an insect nest or a wasp nest.

00:04:26: And when I look at this cytopathic varquose that these flaviviruses make, it always reminds me of the movie Alien.

00:04:33: These cocoons and structures... It's disgusting!

00:04:37: ...I'd like to stay away from flavivirus as much as possible.

00:04:42: West Nile virus is also genetically diverse.

00:04:46: There are nine described lineages but big troublemakers and most common ones are lineage one & lineage two and they are transmitted by a number of different mosquitoes, types of mosquitos but specifically or mostly... ...by cool-x species including Cool-X VPNs.

00:05:07: A little bit about the history.

00:05:08: this virus was discovered in nineteen thirty seven In The West Nile District Of Uganda.

00:05:14: That's where their name comes from.

00:05:17: So They already had human cases there.

00:05:20: In nineteen fifty seven There Was a Human Case Reported In Israel.

00:05:24: In nineteen sixty, the virus was found in sick horses in Egypt.

00:05:29: Nineteen ninety-four it was found Algeria I think.

00:05:33: nineteen ninety six, nineteen ninety seven first time in Romania.

00:05:37: Ninety ninety seven in Czech Republic.

00:05:40: and until nineteen ninety nine this virus is found Africa parts of Europe to Middle East and part Asia as well Australia but not found America's.

00:05:55: And then in nineteen ninety-nine something interesting happened.

00:05:59: It showed up in New York.

00:06:02: Initially birds started dying, and there were unexplained human and cephalitis cases And it took a while until people made the connection.

00:06:16: Initially, their idea was that encephalitis cases might be caused by St.

00:06:20: Louis Encephalaides virus which is a virus that's similar and that circulates in North America.

00:06:27: but turned out this was new virus and the bird infections, the bird deaths... ...and human encephalitis cases were connected.

00:06:38: Then they started to spread from New York westward.

00:06:42: In nineteen ninety-nine, there were relatively few cases.

00:06:44: I think sixty two or something like that reported in two thousand.

00:06:48: even fewer is around twenty.

00:06:50: we're officially reported Two thousand one sixty round sixty cases again But you saw the westward movement and then in two hundred two this exploded with four thousand approximately four thousand reported cases and then in two thousand three there were already about ten-thousand reported cases.

00:07:10: In the United States, and the virus basically spread all over the country also spread to Canada to Mexico and so forth.

00:07:24: So since nineteen ninety nine this virus is also present in the Americas.

00:07:29: it's still not clear how the virus gets got to New York.

00:07:32: The isolates there were very closely related to isolates from Israel, I think the idea is that they were larvae of mosquitoes or mosquitos themselves somehow made it on container ships from Europe and from the Middle East to new york And there these mosquito went down to infect humans caused this outbreak also in europe.

00:07:55: the virus continued to spread In two thousand.

00:07:57: four was found in Hungary I believe are the first reports from Austria, two thousand eighteen.

00:08:04: First report in Germany and Switzerland was lucky.

00:08:09: they managed to delay their introduction it seems.

00:08:12: The virus was first found in twenty-twenty-two in Switzerland And the first human case was reported in Switzerland in twenty twenty five.

00:08:21: If you look at sizes of outbreaks there was again a larger outbreak In the US in Texas mostly in the Dallas area In two thousand twelve with two hundred thirty six deaths.

00:08:35: and in Europe he had a very strong season.

00:08:37: Two thousand eighteen was about one thousand five hundred cases across Europe, and one hundred seventy deaths.

00:08:44: And then twenty-twenty four Was another strong year?

00:08:47: In Europe is again around one thousand Five hundred officially reported cases and more than two hundred Thirty deaths.

00:08:54: A little bit about the biology of the virus.

00:08:57: As I mentioned, the virus is mostly spread by cool ex mosquitos.

00:09:00: in many cases that's Cool Ex pipians which are a very common mosquito species In Europe and North America The reservoirs mostly birds including songbirds And in these animals the virus replicates to very high titers upto ten million particles per milliliter blood or higher.

00:09:25: And when it replicates that much and these animals then get bitten by another mosquito, the mosquitos becomes infected.

00:09:31: They can transmit their virus on them.

00:09:33: if they count of viruses is too low in the blood the mosquitoes don't get infected... ...and there's no onward spread.

00:09:41: I'll get to this in a second.

00:09:43: Some bird species actually die from these infections.

00:09:48: That includes crows, ravens but also birds of prey Oals and so on, they can be pretty susceptible.

00:09:58: And the virus is pretty pathogenic there which is bad because some of these animals are relatively rare and endangered.

00:10:07: There's other birds that also replicate the virus to very high titers and spread it but don't have a lot of symptoms.

00:10:14: The idea is one of the main spreaders in North America is American Robin and in Europe the house sparrow probably is involved in spreading the virus as well.

00:10:27: But this virus, it's very promiscuous can also infect reptiles.

00:10:32: has been found in crocodiles, alligators even snakes which are crazy!

00:10:38: And they can also affect amphibians like frogs.

00:10:41: It also affects a whole range of mammals countless species.

00:10:46: I think that most interesting finding.

00:10:48: A killer whale was infected and unfortunately died of the infection.

00:10:54: And where we see a lot of issues are humans, of course... ...and horses!

00:11:01: Of course humans care about horses.

00:11:02: so cases in horses usually also very prominently flagged.

00:11:08: Humans & Horses or most other mammals.

00:11:12: what do you call dead end hosts?

00:11:16: So we get infected, the horses get infected.

00:11:21: The horse might be sick but the virus doesn't replicate enough in our blood and there's not enough virus to get more mosquitoes infected.

00:11:30: so there is no human-to-human transmission or horse-to–horse transmission via mosquitos.

00:11:35: that why this is called dead end host I mentioned earlier.

00:11:39: often in birds you have ten million virus particles per milliliter of blood.

00:11:45: in horses and humans that's more than a hundred to maybe thousand particles per milliliter range.

00:11:51: And so, there is no onward transmission from us or from other mammals.

00:11:59: A little bit about when these infections occur.

00:12:04: In countries with warmer climate mosquitoes are active the whole year So infection happens all year but often also when there is enough rain to support mosquito populations, while in North America and Europe the cases usually occur.

00:12:20: In the summer month because that's where a lot of mosquitoes are around.

00:12:26: Let's talk about disease.

00:12:28: it starts with a bite from a mosquito you get infected And then an incubation time typically two-to eight days.

00:12:37: In most cases, nothing happens.

00:12:39: Eighty percent of infections are asymptomatic but twenty percent are symptomatic and typical symptoms include fever headache warm-eating.

00:12:50: so there's GI tract involvement rash and myocarditis infection on the heart or the heart muscle.

00:13:00: And in about one percent of cases The central nervous system is involved and this can lead to encephalitis or meningitis with symptoms like stiff neck, confusion, seizures.

00:13:14: And that's when it gets dangerous.

00:13:15: about ten percent of people who have the CNS involvement die from infection so these are serious infections in their CNS environment.

00:13:27: There is a number risk factors.

00:13:29: age is a big risk factor.

00:13:31: The younger you're the less likely it is that you die of West Nile virus or get encephalitis and the risk really starts to increase significantly with age.

00:13:45: It's actually kind going up in a linear way but above the age of sixty, the risk for severe infection is relatively high.

00:13:56: Of course underlying health conditions are also a risk factor.

00:13:59: And then there an interesting thing.

00:14:01: we talked about HAV a while ago.

00:14:04: And one of the receptors of HAV is CCR-V, the chemokine receptor and there are people who have mutations there, deletions.

00:14:17: these are called CCR five delta-thirty two.

00:14:21: If you had this deletion then both your chromosomes were basically resistant to HAV and that's a small proportion of the European population, for example.

00:14:34: And you'd think this is great!

00:14:37: For HIV?

00:14:37: That IS great!

00:14:39: The problem is... ...that it's pretty big risk factor in Western Lovirus infections.

00:14:47: So when you have these CCR-V Delta-XI mutations mutation has much higher risks than getting a severe West Nell infection.

00:14:56: but of course you can't get HIV.

00:15:00: Mosquito bites are not the only way to get infected with West Nile.

00:15:05: There also cases where the virus was spread by a blood transfusions, organ transplants.

00:15:11: these all rear but they have been described.

00:15:13: and then there's also mother-to-child or mother-of-feet transmission.

00:15:18: that can happen during pregnancy.

00:15:20: this can happened in delivery and it happens during breastfeeding.

00:15:27: we talked about horses get infected with West Nile as well.

00:15:33: And with horses, the case fatality rate is even higher.

00:15:36: about forty percent of horses that got infected with west nile die.

00:15:41: They often develop neurological symptoms.

00:15:44: those can include paralysis or staggering dream or even blindness and Of course That's highly problematic As well because horses are companion animals.

00:15:55: in a way there you could say livestock but I guess it's more companion animal.

00:16:02: They're very expensive and so people worry a lot about horses if they own horses, And this is big issue too.

00:16:10: There are no treatment for western animals not humans or horses.

00:16:14: there are no specific antiviral medications.

00:16:17: It has no specific therapy.

00:16:19: i can treat the symptoms but not the virus infection itself.

00:16:24: For humans also no vaccine.

00:16:26: Interestingly There are several vaccines for horses, so the horses can be protected.

00:16:33: But those vaccines I guess would also work for humans but they haven't made it into human use or of course its much more complicated to develop and get a human vaccine licensed than a veterinarian vaccine.

00:16:47: But hypothetically these horse vaccines could work in humans too.

00:16:52: The only effective way prevent West Nile is mosquito control.

00:16:57: In New York, for example there is a mosquito control program.

00:17:00: Mosquitoes get screened from west Nile and if there's an increase in western activity the streets gets sprayed with mosquito spray And If There Is An Increase in Western Electivity Streets Get Sprayed With Insecticide.

00:17:14: That Brings The Mosquito Population Down.

00:17:17: There are some places that do it, others don't.

00:17:20: But in general you can also protect yourself by wearing long pants and long sleeves or use mosquito repellent.

00:17:29: but thats basically the only thing to avoid westerners to avoid bites of mosquitos.

00:17:36: Thats is for today.

00:17:39: That was another virus that could ruin your vacation even if u dont go anywhere during your summer holiday And we'll see if you continue this mini-series about viruses that are spread by mosquitoes during vacation time.

00:17:55: As always, If you have any questions comments or concerns please write an email to virological at podcastjoach.com and if you like the podcast can also support us on Steady.

00:18:07: Thanks for listening in!

00:18:08: Until next week Bye.

00:18:18: you'll find a link in the show notes.

00:18:20: And don't forget to follow and leave a review on your favorite podcast app, Podcastwerkstatt!

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