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.
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.
