#18,535
While the world remains focused on two relatively new H5N1 genotypes (B3.13 & D1.1) circulating in North America, there are literally hundreds of other genotypes of H5Nx evolving and adapting - mostly out of our view - around the globe.
At the same time, there are hundreds of other influenza subtypes - many also with zoonotic potential - evolving and reassorting at a furious rate. The CDC's IRAT list only lists 25, but it is far from complete.
While any of them could suddenly assume the poll position in the race to the next pandemic, the H5N6 virus - circulating in China since early 2014 - is one that we watch with considerable interest.
Of 92 human infections reported so far by China, about half have died.
Like with H5N1, there are a lot of H5N6 variants, with some being far more virulent than others. And like H5N1, new genotypes (and subclades) of H5N6 continue to emerge and evolve.
The evolution of H5 and H7 viruses around the world has often been enhanced by reassortment with LPAI H9N2, which has frequently lent its internal genes to H7N9, H5Nx, and many other flu viruses (see Here, Here, Here, and Here)
All of which brings us to a new report, published this week in Transboundary & Emerging Diseases, which describes two new genotypes of H5N6 recently isolated in China, with one carrying the internal genes from LPAI H9N2 demonstrating worrisome signs of mammalian adaptation.
I've only included the abstract (reformatted for readability) and a brief excerpt from the discussion, so follow the link to read the report in its entirety. I'll have a bit more after your return.
Manlin He, Lina Liu, Jinglei Hu, Zhenjun Wang, Zhendong Guo, Xiaohan Wang, Yongyang Sun, Shaowen Shi, Wenhao Ren, Yuxing Wang … See all authors
First published: 06 January 2025 https://doi.org/10.1155/tbed/6252849
Academic Editor: Makoto Ozawa
Abstract
The H5N6 avian influenza virus (AIV) is constantly undergoing recombination and evolution with other subtypes of AIV, resulting in various types of recombinant H5N6 viruses. However, the risk to human public health of different recombinant types of H5N6 viruses remains unclear.
Recently, two types of different recombinant H5N6 viruses were isolated from chickens.
- One of the viruses possessed six internal genes originating from H9N2, named A/Chicken/Hubei/112/2020 (H5N6) (abbreviated 112);
- the other virus possessed PB2, PB1, PA, and NP originating from H5N1, while the M and NS genes were derived from H9N2, named A/Chicken/Hubei/125/2020 (H5N6) (abbreviated 125).
Here, we investigated the receptor binding properties, pathogenicity, and transmissibility of the two H5N6 AIVs.
The results showed that 112 and 125 could bind α-2,3-linked sialic acid receptor (avian-like receptor) and α-2,6-linked sialic acid receptor (human-like receptor).
However, 125 and 112 showed different pathogenicity in mice. Mice infected with 125 lost only a slight body weight and all survived, while mice infected with 112 lost weight rapidly and all died within a week of infection.
Furthermore, in the transmission experiment, 125 could only transmit through direct contact, while 112 could transmit not only by direct contact but also by aerosol. The above results indicated that 112 exhibited enhanced pathogenicity and transmissibility compared to 125, suggesting that the H5N6 virus, whose internal genes were derived from H9N2, could pose a greater threat to human health.
Therefore, continuous monitoring of different recombinant H5N6 viruses in poultry should be carried out to prevent their transmission to humans.(SNIP)
In conclusion, H5N6 viruses with recombinant internal genes derived from H9N2 have shown increased pathogenicity and transmissibility. It is of great importance to pay attention to the recombination of internal H9 AIV genes with genes from other AIV subtypes.
Therefore, the continuous evolution of the H5N6 virus is a major concern for both the poultry industry and public health. In particular, the number of human infections with H5N6 has continued to increase in recent years; the reason for this is that H5N6 undergoes genetic recombination and adaptive mutations in mammals, suggesting that the ongoing evolution of H5N6 can increase the risk of human infections.
So far, H5N6 has largely remained a problem largely restricted to China and (to a lesser extent) Laos and Vietnam. It has only rarely been detected in wild and migratory birds, restricting its ability to spread internationally.
But last October, in Transboundary & Emerg. Dis.: The Novel 2.3.4.4b H5N6 HPAI Viruses Isolated From Wild Birds in 2023 Posing a Potential Risk to Human Health, we saw a concerning report suggesting that may be changing.
In December 2023, novel reassortant 2.3.4.4b H5N6 viruses were resurgent in wild birds and domestic ducks in Eastern Asia. The viruses were reassorted with those of currently prevalent 2.3.4.4b H5N1 viruses of wild bird origin worldwide, as well as the H5N6 viruses that caused human infections in 2022 and low pathogenic avian influenza viruses, such as the H9N2 virus, which also contributed internal gene to the novel H5N6 viruses.
Just three weeks ago, in China CDC Weekly: Infection Tracing and Virus Genomic Analysis of Two Cases of Human Infection with Avian Influenza A(H5N6) — Fujian Province, China, we looked at a report that stated:
(H5N6) " . . . has acquired mutations that may enhance human receptor binding affinity, viral replication capacity, pathogenicity, and neuraminidase inhibitor resistance."
None of this guarantees that H5N6 will become the next big pandemic threat. But it should remind us that even if we somehow manage to subdue H5N1, any victory will be short-lived.
Because there are plenty of other novel viruses with zoonotic potential in the queue.
