Wednesday, August 06, 2025

EID Journal: Attachment Patterns of Avian Influenza H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine Mammals, North Atlantic Ocean


Flu Virus binding to Receptor Cells – Credit CDC

#18,826

We've known for over 4 decades that marine mammals (seals, whales, dolphins, etc.) are susceptible to influenza A viruses (see 1984's Are seals frequently infected with avian influenza viruses? by Webster et al.), and over the past 20 years have looked a number of unusual mortality events (UMEs). 

While some outbreaks have likely gone unreported, it wasn't until 2017 that an HPAI H5 virus (H5N8) was detected in marine mammals (see above). The big surge, however, began in 2020, after the changeover from H5N8 to H5N1:
Two Reports On HPAI H5N8 Infecting Marine Mammals (Denmark & Germany)

UK: HAIRS Risk Assessment On Avian Flu In Seals (2022)

Not only have tens of thousands of marine mammals died from HPAI H5 over the past 5 years, there is growing evidence that some species can transmit the virus from mammal-to-mammal (see Nature Comms: Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b HPAI A/H5N1 with PB2 adaptations).

Since 2020 we've seen HPAI H5N1 dramatically increase both its geographic and (avian & mammalian) host range, as well as producing increased neurological manifestations (see Cell: The Neuropathogenesis of HPAI H5Nx Viruses in Mammalian Species Including Humans) in some hosts.

Simply put, the H5Nx virus of today is a far cry from the H5Nx of 2005, or even 2019. And those changes are likely to continue. 

Today we've a research paper published in the EID Journal which suggest that these changes may be linked to changing viral cell tropism favoring lower respiratory tracts in some mammals.  

Among their key findings:

  • Researcher found both the 2005 and 2022 H5N1 viruses attached readily to upper respiratory tract tissues in seals
  • But the 2022 clade 2.3.4.4b virus showed significantly increased affinity for  lower respiratory tract tissues as well 
  • Additionally, seals showed greater susceptibility than cetaceans (porpoises and dolphins)

Due to its length, I've only posted the abstract a few excerpts. Follow the link to read it in its entirety.  I'll have a bit more after the break. 

Attachment Patterns of Avian Influenza H5 Clade 2.3.4.4b Virus in Respiratory Tracts of Marine Mammals, North Atlantic Ocean

Syriam Sooksawasdi Na Ayudhya1, Lonneke Leijten, Willemijn F. Rijnink, Monique I. Spronken, Thijs Kuiken, Lisa Bauer2, and Debby van Riel2

Abstract

Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infections have caused substantial mortality events in marine mammals in recent years. We hypothesized that the high number of infections and disease severity could be related to cell tropism in respiratory tracts. Therefore, we examined the attachment pattern of an H5N1 clade 2.3.4.4b virus (H52022) as a measure for cell tropism in the respiratory tracts of harbor seals, gray seals, harbor porpoises, and bottlenose dolphins and compared it with an H5N1 clade 2.1.3.2 virus (H52005) and a human seasonal H3N2 virus using virus histochemistry.

Both H5 viruses attached abundantly to olfactory and respiratory mucosa in the upper respiratory tract of both seal species. H52022 attached more abundantly than H52005 to epithelial cells in the lower respiratory tract of all species. The observed attachment possibly explains the susceptibility of marine mammal species for recent H5N1 viruses and the observed development of severe disease.

(SNIP)

The ability of HPAI H5N1 clade 2.3.4.4b viruses to infect and cause severe disease in a broad range of mammal species has not been previously observed with other avian influenza A viruses (3,34).

The attachment pattern in the respiratory tract of marine mammals of H5N1 clade 2.3.4.4b virus, and whether that pattern differs from the attachment pattern of previously circulating H5 viruses from different clades, is unknown. Therefore, we compared the attachment pattern of a 2022 H5N1 clade 2.3.4.4b virus, a 2005 H5N1 clade 2.1.3.2 virus, and a seasonal human H3N2 virus in the respiratory tracts of marine mammals commonly found in the North Atlantic Ocean: harbor seals, gray seals, harbor porpoises, and bottlenose dolphins.

       (SNIP)

Discussion

We describe the attachment patterns of HPAI H5N1 viruses in the respiratory tracts of common North Atlantic marine mammals. Our study revealed that avian H5 viruses attach abundantly to the upper respiratory tract of harbor seals and gray seals. In the lower respiratory tract of harbor seals, gray seals, and harbor porpoises, the recent H5N1 clade 2.3.4.4b virus attaches more abundantly than an H5N1 clade 2.1.3.2 virus from 2005.
(SNIP)
Several studies have shown that recent H5N1 clade 2.3.4.4b viruses, including bovine isolates, preferentially bind to α2,3-linked sialic acid receptors (41,4547). The variability in attachment between the 2 H5N1 virus clades in our study are therefore likely not the result of a receptor switch to 2,6-linked sialic acid but potentially because of the amino acid differences in or close to the receptor-binding site, known to affect receptor specificity or affinity. However, the exact role of the individual amino acid positions remains to be investigated
Both HPAI H5N1 viruses (either of clade 2.3.4.4b or clade 2.1.3.2) and H3N2 virus attach to olfactory mucosa in the nasal cavity of gray and harbor seals. Neurologic complications are regularly observed in marine mammals infected with H5 viruses, and virus can be detected in high titers in the brain (19,21,23,24,28).
How H5 viruses enter the central nervous system remains unclear, but observations suggest that the viruses can enter the central nervous system via the olfactory nerve in seals, as observed in experimentally inoculated ferrets (4850). However, HPAI H5N1 viruses can also invade the central nervous system in ceteceans, which lack a olfactory mucosa, so neuroinvasion likely could also occur via other cranial nerves or the hematogenous route (28).

In conclusion, our study highlights changes in the attachment pattern of a recent HPAI H5N1 clade 2.3.4.4b virus compared with H5N1 clade 2.1.3.2 virus from 2005 in the respiratory tracts of 4 marine mammal species that could lead to more efficient transmission and more severe disease.
That finding, together with the recent increase in HPAI H5N1–associated deaths in marine mammals worldwide, emphasizes the need for increased avian influenza surveillance and research in such marine mammal species to limit illness and deaths and help protect both animal and human health.

Dr. Sooksawasdi Na Ayudhya is an instructor and researcher at the Faculty of Veterinary Science, Prince of Songkla, Songkhla, Thailand. Her main interests are pathogenesis and molecular epidemiology of viral infectious diseases and viral emerging infectious diseases in humans and animals.
       (Continue . . . )


Not so very long ago conventional wisdom held that for HPAI H5N1 to pose a genuine human pandemic threat, it would need to change its preference for avian α2,3-linked receptor cells to mammalian α2,6-linked receptor cells.

And while that may still be true, there are hints in this study that other genetic changes in (or near) the RBD (Receptor Binding Domain) of the virus may enable avian α2,3 binding viruses to better infect mammals.

We've seen other examples of `permissive mutations' that can counteract the effects of existing genetic traits (see Virus Research: A 15-year Study of Neuraminidase Mutations and the Increasing of S247N Mutation in Spain). 

Today's report is reminder that the HPAI H5 virus of today is not the same H5N1 virus that threatened - but failed - to produce a pandemic 20 years ago. 

If the past 18 months have taught us anything, it is that the HPAI H5Nx virus is rapidly evolving on multiple fronts - and while that doesn't guarantee a more formidable virus in the future - the trajectory we are seeing is far from reassuring.