Monday, November 14, 2022

Preprint: Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America



As we've discussed many times in the past (see Differences In Virulence Between Closely Related H5N1 Strains), the subtype (e.g. H5N1, H7N9, H5N6, etc) of an influenza virus is only a general descriptor, and within each subtype there can be dozens of clades, and genotypes, with varying levels of virulence and transmissibility.

The H5N1 clade virus circulating in Europe and North America today is a far cry from the neurovirulent clade H5N1 virus that circulated in China a decade ago, or the clade 1 viruses which appeared in 2003 - mostly in Vietnam, Cambodia & Thailand.

As result, over the past 2 decades more than 5 dozen H5, H9, H1, H3, and H7 candidate vaccine viruses (CVVs) have been selected by WHO for development. Many of these older CVVs were for viruses that no longer circulate in the wild, having been supplanted by newer versions.

But even within the current-day clade, there can be a great deal of diversity, which may help  explain why we've seen some severe mammalian infections (see partial list below), while the known human infections with this clade have been mild or asymptomatic. 

Canada: First Detection Of H5N1 In A Black Bear With Avian H5N1
Maine: Seal Deaths Linked To Avian H5N1
Quebec: Seal Deaths Linked To Avian H5N1
Ontario: CWHC Reports HPAI H5 Infection With Severe Neurological Signs In Wild Foxes (Vulpes vulpes)

As migratory birds spread the HPAI H5 virus, the virus encounters other endemic avian viruses, and through reassortment (see below), new viral combinations are created. Most are evolutionary failures, but some are biologically `fit' enough to survive, and even thrive. 

These new genotypes can vary greatly in their ability to infect avian and non-avian hosts, and in their virulence. The longer a subtype like H5N1 remains in the wild bird population, and the further it travels, the more opportunities it will have to reinvent itself. 

Over the past year we've seen a remarkable geographical expansion of HPAI H5N1 from Europe to North America, and an Unprecedented `Order Shift' In Wild Bird H5N1 Positives In Europe & The UK, providing the virus with numerous genetic building blocks with which to generate new genotypes. 

While our current HPAI H5N1 virus hasn't demonstrated the ability to jump to humans the way some of its more virulent ancestors did, the virus continues to mutate, and its future course and impact is unpredictable. 

All of which brings us to a preprint, which finds that the longer HPAI H5N1 has circulated in North America, the more genotypes it has generated. And as might be expected, some of those genotypes are far more virulent in mammals than others. 

Because this is a highly detailed report, and I can't possibly do it justice here. I've only posted the abstract below, you'll want to follow the link to read it in its entirety.  I'll have a postscript after you return. 

Rapid evolution of A(H5N1) influenza viruses after intercontinental spread to North America

Ahmed Kandeil, Christopher Patton, Jeremy Jones, Trushar Jeevan, and 19 more

This is a preprint; it has not been peer reviewed by a journal.

This work is licensed under a CC BY 4.0 License


Highly pathogenic avian influenza A(H5N1) viruses of clade underwent an explosive geographic expansion in 2021, with the viruses being detected in wild birds and domestic poultry across Asia, Europe, and Africa. In 2022, viruses of this clade were detected in North America, signifying further intercontinental spread.
Here, we show that the western movement of clade was quickly followed by reassortment with local circulating viruses, resulting in the acquisition of novel polymerase gene cassettes.
These reassortant A(H5N1) viruses are genotypically and phenotypically diverse, with many causing severe disease with dramatic neurologic involvement, in mammals. The proclivity of the current A(H5N1) virus lineage to reassort and target the central nervous system warrants concerted planning to combat the spread and evolution of the virus within the continent and to mitigate the impact of a potential influenza pandemic that could originate from similar A(H5N1) reassortants.

          (Continue . . . )


Despite the differences in virulence, none of these HPAI H5 viruses tested appear to be ready for prime time.  So far, they bind preferentially to avian alpha 2,3 receptor cells found in the gastrointestinal tract of birds, not the alpha 2,6 receptor cells most commonly found in the human respiratory system.

The authors write:

From a public health perspective, the increased pathogenicity of the reassortant A(H5N1) viruses is of significant concern. However, this is tempered by the avian virus–like characteristics of the viruses with respect to their receptor binding preference and their pH of HA activation. These characteristics probably need to change to enable sustained human-to-human transmission, although only a few amino acid changes among various influenza proteins are needed to switch these properties during adaptation in mammals.

While the future evolution of these avian viruses is unknowable - and there may even be a `species barrier' that prevents an H5 virus from sparking a human pandemic (see Are Influenza Pandemic Viruses Members Of An Exclusive Club?) - public health agencies like the CDC, ECDC, and WHO are taking the threat seriously. 

Last month the ECDC released a 32-page guidance document on testing and detection of zoonotic influenza viruses in humans, while CDC's Guidance can be found HERE.

Meanwhile, Mother Nature's laboratory is open 24/7, where its grand field experiment never ends.