HPAI H5N5: A Variation On A Theme - Cell Reports: Transatlantic Incursions of HPAI H5N5 (Jul 2024)

[Michael Coston]

HPAI H5N5: A Variation On A Theme

HPAI H5N5 WAHIS Updates for 2024




#18,008

This week WOAH reported (see below) more detections of HPAI H5N5 (clade 2.3.4.4b) virus in raccoons from Nova Scotia and Prince Edward Island. The virus had previously been detected in wild birds, but turned up in dead raccoons on Prince Edward Island a year ago (see CIDRAP Report Canada reports first H5N5 avian flu in a mammal).

EPIDEMIOLOGICAL COMMENTS

We report additional cases of highly pathogenic avian influenza Fully Eurasian H5N5 (2.3.4.4b) virus in raccoons from Nova Scotia and Prince Edward Island. Outbreaks are reported by province/territory. The geographical marker is on the capital. For detailed and current information on high pathogenicity avian influenza cases in wildlife, please consult : http://www.cwhc-rcsf.ca/avian_influenza.php.​

While our biggest concern is currently HPAI H5N1, we've seen closely related H5N3, H5N4, H5N5, H5N6, and H5N8 viruses - the product of H5N1 reassorting with other LPAI viruses - infecting both birds and mammals around the globe.

The H5N5 avian subtype first came to light in a 2011 report (see EID Journal: Novel H5N5 Avian Influenza Detected In China), which described the isolation of two novel reassortant HPAI H5N5 viruses from apparently healthy domestic ducks in Eastern China.

Several of the same authors wrote about additional isolates of the H5N5 virus in the journal Veterinary Microbiology (see Characterization of three H5N5 and one H5N8 highly pathogenic avian influenza viruses in China), that were isolated in China in 2009-10, suggesting that the first detection wasn’t a fluke.​

Although we have looked at the the threat and evolution of HPAI H5N5 a number of times in the past (see here, here, and here), recent changes to clade 2.3.4.4b viruses probably make findings before 2021 less relevant.

In June of 2022, in Norwegian Veterinary Institute : HPAI Detected In Arctic (Svalbard) For the First Time, both H5N1 and H5N5 were detected (see press release below).

Bird flu causes high mortality among wild birds in Norway​​

Published 21.06.2022 Modified 22.06.2022

In recent weeks, an abnormally high number of sick and dead birds has been observed in several places along the Norwegian coast. In May and June, the Veterinary Institute detected highly pathogenic avian influenza (HPAI) of subtype H5N5 in sea eagles, ravens, crows and several gull species in Troms and Finnmark. In the North Sea and along the coast in Rogaland, a high number of dead ospreys have been observed, and HPAI of the subtype H5N1 has been detected in several of these. In addition, HPAI has been detected in wild birds in Oslo, Bergen and several places in Trøndelag and Møre og Romsdal.​

In the most recent ECDC/EFSA Quarterly Avian Influenza Overview Dec 2023 - Mar 2024, there were several mentions of HPAI H5N5, including:

• Subtype A(H5N5), genotype EA-2021-I, which has persistently been detected in Norway since the 2021–2022 epidemiological year, has since September 2023 spread to Iceland, the United Kingdom, Greenland and Germany, and – besides infecting wild birds – infected red foxes in Norway. A(H5N5) was also detected in Faroe Islands and Japan during the current epidemiological year.

• Unlike the mammalian infections reported in Europe during the summer months in 2023, mainly caused by the EA-2022-BB genotype, the recent A(H5) viruses identified in wild mammals belonged to different A(H5N1) and A(H5N5) genotypes. The detection of A(H5N5) virus in two red foxes from Norway represents the first detection of this subtype in mammals in Europe.

HPAI H5 is a highly promiscuous virus, capable of reassorting with a variety of other influenza A viruses. It continually spins off new genotypes (including new subtypes) as it spreads, some potentially being more dangerous than others.

It is for this reason there is so much concern about HPAI H5 spilling over into pigs, which would give it access to a wide array of swine and human viruses.​

But other species, including humans, marine mammals, mink, and even dogs and cats could serve as an effective `mixing vessel'.

Six years ago, HPAI H5N8 was the dominant H5 subtype, but was supplanted by H5N1 in 2020. It is entirely possible that we could seen another shift - from H5N1 to H5N5, or H5N6, or to some other n-type, in the months or years ahead.​

And while clade 2.3.4.4b is currently in the driver's seat, we've seen a resurgence in clade 2.3.2.1c in Cambodia over the past year, and last week the FAO warned of a Reassortment Between H5N1 Clade 2.3.4.4b & Clade 2.3.2.1c Viruses In Mekong Delta Region.

While we expect all influenza A viruses to change over time, HPAI H5 seems to be working overtime.​

Which is why we need to be prepared for more surprises.​


https://afludiary.blogspot.com/2024/04/hpai-h5n5-variation-on-theme.html

 

[Michael Coston]

WAHIS: More Reports of HPAI H5N5 in Canada





Canadian HPAI- WILDLIFE DASHBOARD - Mammalian H5

#18,060

Yesterday WOAH reported more detections of HPAI H5N5 (clade 2.3.4.4b) virus in small mammals from Nova Scotia and Prince Edward Island - and for the first time - in a bird (an American Crow) outside of the Atlantic Provinces (in Quebec).

This H5 variant had previously been detected in wild birds, but turned up in dead raccoons on Prince Edward Island a year ago (see CIDRAP Report Canada reports first H5N5 avian flu in a mammal).​

A month ago, in HPAI H5N5: A Variation On A Theme, we looked at more recent reports of H5N5 being detected in birds, and wildlife (primarily raccoons and red foxes) on PEI. Today, we've a WAHIS updateadding 4 more detections (3 striped skunks, 1 raccoon) to the list (n=13).

EPIDEMIOLOGICAL COMMENTS

We report additional cases of highly pathogenic avian influenza Fully Eurasian H5N5 (2.3.4.4b) virus in raccoons from Nova Scotia and Prince Edward Island. Outbreaks are reported by province/territory. The geographical marker is on the capital. For detailed and current information on high pathogenicity avian influenza cases in wildlife, please consult : http://www.cwhc-rcsf.ca/avian_influenza.php.​

While 13 H5N5 detections doesn't sound like much, it does represent nearly 7% of Canada's total (n=189) mammalian wildlife detections of HPAI over the past 3 years.

Since surveillance for wildlife infection is very limited, we can assume a lot of cases go unreported.​

So far, all of Canada's H5N5 cases have been clustered in the NS/PEI region, but today we have the following WAHIS report of H5N5 detected in a wild bird in Quebec.

EPIDEMIOLOGICAL COMMENTS

We report the first detection of a wild bird infected with highly pathogenic fully Eurasian H5N5 (2.3.4.4b) avian influenza viruses outside of the Atlantic provinces (Québec). This Event is the continuation of Event #4754, where we had reported previous occurrences of H5N5 in Nova Scotia, New Brunswick and Prince Edward Island . Outbreaks are reported by province/territory. The geographical marker is on the capital.
​

For detailed and current information on high pathogenicity avian influenza cases in wildlife, please consult : http://www.cwhc-rcsf.ca/avian_influenza.php Wildlife surveillance as well as the Canadian Avian Influenza Surveillance System (CanNAISS) activities for poultry are ongoing in Canada. According to Article 10.4.1.4. of the Terrestrial Animal Health Code, Member Country should not impose bans on the international trade of poultry commodities in response to notification of infection with any Influenza A viruses in birds other than poultry.​

To date, Canada has reported 38 H5N5 detections in wild birds. Thus far, no H5N5 reports have been submitted by the United States to WOAH.

Although our biggest concern is currently HPAI H5N1, over the years we've seen closely related H5N3, H5N4, H5N5, H5N6, and H5N8 viruses - the product of H5N1 reassorting with other LPAI viruses - infecting both birds and mammals around the globe.

We saw HPAI H5N5 surface a number of times during the first major HPAI H5N8 epizootic of 2016-2017 (see ESA: Epidemiological Update On H5N8/H5N5 In Europe), but it has never really established itself the way that H5N1, H5N8, and (to a lesser extent) H5N6 have.

But the changes to the H5 clade 2.3.4.4b lineage over the past 3 years may be changing that dynamic. Over the past 90 days WAHIS has published a noticeable uptick in H5N5 reports from around the globe (see below).



While these reports may be little more than `viral chatter', and H5N5 may never become a serious player, the superpower of influenza is its ability to continually reinvent itself.

Ten years ago, H5N1 was arguably the biggest HPAI threat, but it was supplanted by H5N8 in the middle of the last decade, and then (ever so briefly) by H5N6, before roaring back in 2021.​

It is entirely possible that we could seen another shift - from H5N1 to H5N5, or H5N6, or to some other n-type, in the months or years ahead. The virus has an large - and growing - array of diverse hosts to inhabit, and no lack of genetic diversity on which to draw.


All reasons why we should fully expect to see additional surprises in the future.

https://afludiary.blogspot.com/2024/05/wahis-more-reports-of-hpai-h5n5.html
​

 

[Michael Coston]

Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammals




#18,190



While HPAI H5N1 has captured most of our attention, for the past 14 months we've been following another clade 2.3.4.4b HPAI H5 subtype - H5N5 - which has been making inroads in both birds and mammals in (mostly) Eastern Canada.

Although we've seen reports of H5N5 in European birds, it was detected in dead raccoons on Prince Edward Island a little over a year ago (see CIDRAP Report Canada reports first H5N5 avian flu in a mammal).​

Last April, in HPAI H5N5: A Variation On A Theme, we looked at more recent reports of H5N5 being detected in birds, and wildlife (primarily raccoons and red foxes) on PEI.

We followed up in May with WAHIS: More Reports of HPAI H5N5 in Canada, which added more mammalian detections, and the first detection (in an American Crow) outside of the NS/PEI region (in Quebec).

While our biggest concern remains HPAI H5N1, over the years we've seen closely related H5N3, H5N4, H5N5, H5N6, and H5N8 viruses - the product of H5N1 reassorting with other LPAI viruses - infecting both birds and mammals around the globe.

Today we've a lengthy study, published in Cell Reports that examines how this subtype likely made it to North America, its impact on mammals, and its potential risks going forward.

I've only posted some excerpts from a fascinating report, so follow the link to read it in its entirety. I'll have a brief postscript after the break.

Multiple transatlantic incursions of highly pathogenic avian influenza clade 2.3.4.4b A(H5N5) virus into North America and spillover to mammals

Cassidy N.G. Erdelyan 1 14, Ahmed Kandeil 2 3 14, Anthony V. Signore 1, Megan E.B. Jones 4, Peter Vogel 5, Konstantin Andreev 2, Cathrine Arnason Bøe 6, Britt Gjerset 6, Tamiru N. Alkie 1, Carmencita Yason 7, Tamiko Hisanaga 1, Daniel Sullivan 1, Oliver Lung 1 8, Laura Bourque 4, Ifeoluwa Ayilara 1, Lemarie Pama 1, Trushar Jeevan 2, John Franks 2, Jeremy C. Jones 2, Jon P. Seiler 2…Yohannes Berhane 1 12 13 15Show more

https://doi.org/10.1016/j.celrep.2024.114479Get rights and content
Under a Creative Commons license
open access​

Highlights​

• Seabirds likely enabled multiple incursions of A(H5N5) virus from Europe to Canada​

• Some A(H5N5) viruses possessed the mammalian adaptation marker PB2-E627K​

• A(H5N5) viruses demonstrated rapid 100% mortality and some transmission in ferrets​

• A(H5N5) viruses preferred avian virus receptors and are sensitive to NA inhibitors​

Summary​

Highly pathogenic avian influenza (HPAI) viruses have spread at an unprecedented scale, leading to mass mortalities in birds and mammals. In 2023, a transatlantic incursion of HPAI A(H5N5) viruses into North America was detected, followed shortly thereafter by a mammalian detection. As these A(H5N5) viruses were similar to contemporary viruses described in Eurasia, the transatlantic spread of A(H5N5) viruses was most likely facilitated by pelagic seabirds.

Some of the Canadian A(H5N5) viruses from birds and mammals possessed the PB2-E627K substitution known to facilitate adaptation to mammals. Ferrets inoculated with A(H5N5) viruses showed rapid, severe disease onset, with some evidence of direct contact transmission.

However, these viruses have maintained receptor binding traits of avian influenza viruses and were susceptible to oseltamivir and zanamivir. Understanding the factors influencing the virulence and transmission of A(H5N5) in migratory birds and mammals is critical to minimize impacts on wildlife and public health.

(SNIP)​

Mutations associated with mammalian adaptation A(H5N5) viruses isolated from both mammals and birds had mutations associated with mammalian adaptation. Viruses from two mammals (A/Raccoon/PEI/FAV-0199-1/2023 and A/Striped_Skunk/PEI/FAV-0210-1/2023) and two gulls (A/Great_Black-Backed_Gull/NS/FAV-0263-8/2023 and A/Herring_Gull/NS/FAV-0263-6/2023) had the mammalian adaptive E627K mutation in the polymerase basic protein (PB2). PB2-E627K yields more efficient IAV replication in mammalian cells. Viruses from the infected mammals appeared to have acquired the E627K mutations independently as they were phylogenetically distinct from one another and clustered with other A(H5N5) viruses containing PB2-E627, while the two gulls most likely acquired it from a common source due to sequence similarity (Figure S1).

Some viruses from Sable Island had mutations not seen in other A(H5N5) isolates. A/Black-Legged_Kittiwake/NS/FAV-0264-11/2023 had two mutations previously associated with increased virulence in mammals, PB2-I292V and PB1-F2-N66S. While no other viruses appeared to have descended from this specific virus, it was more closely related to the A(H5N5) from the only skunk sample (A/Striped_Skunk/PEI/FAV-0210-1/2023).

Other experimentally supported amino acid substitutions associated with adaptation in birds and mammals are summarized in Table S1.​

(SNIP)

Risk for mammals​

While infections with IAV containing N5 have been described in seals (H4N5)89 and swine (H10N5),90 to our knowledge there have been no previously reported cases of A(H5N5) infection in mammals.

In the present study, we have 7 confirmed cases of mammalian A(H5N5) infections leading to deaths (4 raccoons, 2 red foxes, 1 striped skunk). While it is concerning that individual mammalian-adaptive mutations were detected in these animals, there was no evidence of mammal-to-mammal transmission. The high proportion of Canadian A(H5N5) detections in mammals (7 of the 41, 17%, total detections) is surprising. In contrast, of the 2,118 Canadian A(H5N1) detections, only 96 were from mammals (4.5%).​

(SNIP)

Although influenza viruses are well studied, many gaps in our knowledge remain. As IAV represents a global risk, intensive surveillance is required, especially in bird species found in migratory stopovers, where mingling of birds from different flyways occurs.

Our data implicate pelagic seabirds in the transatlantic and local Canadian spread of A(H5N5) viruses that have maintained an NA stalk deletion. These viruses have been detected in wild mammals, where markers for mammalian adaptation (PB2-E627K) have been detected. Ferret pathogenesis studies with the EA genotype A(H5N5) viruses demonstrated their high virulence, which is in contrast to the early North American A(H5N1) viruses that required North American segments to induce mortality.

Thus, while A(H5N5) viruses are comparably uncommon, their high virulence and mortality potential demand global surveillance and further studies to untangle the molecular markers influencing virulence, transmission, adaptability, and host susceptibility.​

(Continue . . . )


Since my last update in May one additional mammalian detection (in a red fox) was reported in Nova Scotia (see WAHIS report #5065), and six additional reports in wild birds see WAHIS report #5283 divided between Nova Scotia and Newfoundland and Labrador.

While HPAI H5N5 doesn't appear to be gaining a lot of momentum, it hasn't disappeared either.​

Stay tuned.

https://afludiary.blogspot.com/2024/07/cell-reports-multiple-transatlantic.html
​