Sunday, December 22, 2024

Virus Evolution: Recurring Incursions & Dissemination of Novel Eurasian-origin H5Nx Avian Influenza Viruses in Atlantic Canada


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#18,504

Last August, in Something Winged This Way Comes, we discussed our `knowledge gap' of what evolutionary changes might have occurred over the summer among HPAI H5 viruses in the high latitude summer roosting areas for migratory waterfowl. 

I wrote:

Exactly what returns this fall is unknown, as the virus has had numerous opportunities to reassort or mutate over the summer. We could see something worse, or if we get very lucky, an attenuated threat (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).

And true to form, this fall we've seen two new H5N1 genotypes (D1.1 and D1.2) join the fray, causing numerous outbreaks in poultry, more than a dozen human infections, and apparently causing significant die offs of wild birds across the country.  

These D1.x genotypes are genetically distinct from the B3.13 `Bovine' strain, and have been linked to at least 2 `severe' human infections.  A reminder that HPAI H5 is a constantly moving target. 

But at the same time, we've been tracking another viral interloper - HPAI H5N5 - making inroads both in Europe, and (repeatedly) crossing the Atlantic, and appearing in Eastern Canada (see The Continued Expansion of HPAI H5N5).

New subtypes or new genotypes of the HPAI H5 virus are a product of the H5 virus reassorting with other LPAI viruses - which can occur in both birds and mammals around the globe.  

We've seen reports of H5N5 in European birds going back to 2016, but it was first detected in dead raccoons on Prince Edward Island about 18 months ago (see CIDRAP Report).  Since last May, we've seen increasing reports of its western expansion (see WAHIS: More Reports of HPAI H5N5 in Canada).

Last July, in Cell Reports: Multiple Transatlantic Incursions of HPAI clade 2.3.4.4b A(H5N5) Virus into North America and Spillover to Mammalsresearchers reported finding the mammalian adaptive E627K mutation in a number of samples.

They wrote:

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.

While still a relatively minor player, we've seen increased H5N5 activity in both Europe and the UK in recent months.  To that we can also add the following journal article from Virus Evolution, which describes its repeated introductions into Canada and recent evolutionary changes. 

A link and some excerpts from the report, after which I'll have a bit more. 

Recurring incursions and dissemination of novel Eurasian-origin H5Nx avian influenza viruses in Atlantic Canada
Ishraq Rahman, Cassidy N.G Erdelyan, Anthony V Signore, Ifeoluwa Ayilara, Jordan Wight, Megan E.B Jones, Daniel S Sullivan, Oliver Lung, Tamiko Hisanaga, Sabina I Wilhelm 
Virus Evolution, veae111, https://doi.org/10.1093/ve/veae111
Published: 17 December 2024 

PDF

Abstract

Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards.

This lineage has evolved and diversified over time, with a recent important derivative being the 2.3.4.4b sub-lineage, which has caused significant mortality events in wild bird populations. An H5N1 clade 2.3.4.4b virus was transmitted into North America from Eurasia in 2021, with the first detection being in Newfoundland and Labrador in Atlantic Canada, and this virus and its reassortants then spread broadly throughout North America and beyond.

Following the first 2021 detection, there have been three additional known incursions of Eurasian-origin strains into Atlantic Canada, a second H5N1 strain in 2022 and two H5N5 strains in 2023.

In this study we document a fifth incursion in Atlantic Canada that occurred in 2023 by another H5N5 strain. This strain spread throughout Atlantic Canada and into Quebec, infecting numerous species of wild birds and mammals.

Genomic analysis revealed mammalian-adaptive mutations in some of the detected viruses (PB2-E627K and PB2-D701N) and mutations in the hemagglutinin (HA) and neuraminidase (NA) genes that are associated with enhanced viral fitness and avian transmission capabilities.

Our findings indicate that this virus is continuing to circulate in wildlife, and confirms Atlantic Canada is an important North American entry point for Eurasian IAVs. Continued surveillance and genomic analysis of IAVs detected in the region is crucial to monitor the evolution of these viruses and assess potential risks to wildlife and public health.

          (SNIP)

Conclusions

This study describes the fifth incursion and dissemination of a Eurasian 2.3.4.4b clade H5Nx virus into Atlantic Canada since November 2021. These viruses have been found in a wide range of wild bird species and have been transmitted to mammals. Phylogenetic analyses indicated that this H5N5 strain was a novel introduction from Eurasia and was not the continued spread and dissemination of H5N5 viruses that were detected earlier in 2023.
Several amino acid changes detected in the HA, NA, and PB2 sequences of these H5N5 viruses are known to affect pathogenicity and transmission, HA glycosylation, and the ability to bind to avian receptors.

 The presence of these mutations suggests ongoing selective pressure for adaptation to avian hosts, which may facilitate the rapid spread among wild birds and result in additional spillovers to mammals.

Our findings provide direct evidence that these H5N5 viruses can infect and be transmitted by a broad range of host species, and as such have quickly become globally disseminated.
Continued surveillance of IAVs in wild animals with a focus in high-transmission zones such as Atlantic Canada is crucial to track the evolution of these viruses during their ongoing circulation and to assess potential impacts they may have on wildlife and public health.
         (Continue . . . )

Over the past decade we've seen the rise (and fall) of a highly successful H5N8 virus, followed by the surprise return of a far more capable clade 2.3.4.4b H5N1 virus. 

In the 3 years since H5N1 arrived in North America, the virus has evolved into more than 100 genotypes.  

Globally, H5's diversity is even greater.  Admittedly, most of these variants will fall by the wayside, unable to successfully compete against more biologically `fit' strains.   

Right now, it isn't clear how much of a player H5N5 will turn out to be. For now, however, it appears to be on the ascendant. 

The growing array of H5 viruses circulating globally arguably poses a much greater pandemic threat than it did just a few years ago.  Meaning - even if we somehow manage to suppress or eradicate `bovine H5N1' - there are a number of other H5Nx contenders out there to take its place.

There's an old joke about a tourist asking a NYC cabby, `What’s the best way to get to Carnegie Hall? and the cabby replies, “Practice, practice, practice”.

Unfortunately, our largely passive (`don't test, don't tell')  approach to HPAI over the past year has given HPAI nearly unfettered opportunities to practice; on cattle, humans, cats, and dozens of other peridomestic species. 

Whether or when the virus will ever be ready for Carnegie Hall remains unknown.

But the longer it circulates and the more opportunities it is given to evolve (or reassort), the greater the odds are that a viral prodigy will eventually emerge.