Thursday, February 29, 2024

EID Journal: HPAI A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023


The rapid spread of HPAI H5N1 down the length of South America - which began in the fall of 2022 - brought with it numerous reports of marine mammal die offs (see EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)), along with the loss of hundreds of thousands of wild birds.

Although we've long known that marine mammals (seals, whales, sea lions, otters, etc.) are susceptible to influenza viruses (see UK: HAIRS Risk Assessment On Avian Flu In Seals) - we've never seen anything quite like the losses due to HPAI H5 over the past 16 months in South America.

Along the way we've seen indications that as HPAI H5 has spilled over into marine mammals, it has acquired a number mammalian host adaptations.  Small amino acid changes that make it more suitable for carriage in non-avian species. 

In last November's EID Journal: Highly Pathogenic Avian Influenza A(H5N1) from Wild Birds, Poultry, and Mammals, Peru, the authors cited:

2 mutations in the polymerase basic 2 protein (Q591K and D701N) associated with mammal adaptation were identified only in sequences from sea lions in Peru and from 1 human case in Chile.

Today we've a research letter, published in the EID Journal, from University of California, Davis, and the National Institute of Agricultural Technology (INTA) in Argentina, that characterizes the full genome of the HPAI H5N1 virus collected from samples taken from four sea lions, one fur seal and a tern last August.

They found the same two mutations (Q591K and D701N) described above in the Peruvian study, along with others, which suggest that the virus has adapted to mammalian hosts, while still retaining the ability to infect birds. 

They authors also state that, based on the available evidence, `. . . it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region.'

You'll find a less technical summary in the following press release from the UNIVERSITY OF CALIFORNIA - DAVIS, followed by a link to, and some excerpts from the full EID article. 

Avian influenza virus is adapting to spread to marine mammals

Findings raise concerns about wildlife conservation and ecosystem health

The highly pathogenic avian influenza virus H5N1 has adapted to spread between birds and marine mammals, posing an immediate threat to wildlife conservation, according to a study from the University of California, Davis, and the National Institute of Agricultural Technology (INTA) in Argentina.

The study, published in the journal Emerging Infectious Diseases, is the first genomic characterization of H5N1 in marine wildlife on the Atlantic shore of South America.


Genome sequencing revealed that the virus was nearly identical in each of the samples. The samples shared the same mammal adaptation mutations that were previously detected in a few sea lions in Peru and Chile, and in a human case in Chile. Of note, the scientists found all these mutations also in the tern, the first such finding.

“This confirms that while the virus may have adapted to marine mammals, it still has the ability to infect birds,” said first author Agustina Rimondi, a virologist from INTA. “It is a multi-species outbreak.”

We know this because the virus sequence in the tern retained all mammal-adaptation mutations. Such mutations suggest a potential for transmission between marine mammals.

          (Continue . . . )

Research Letter
Highly Pathogenic Avian Influenza A(H5N1) Viruses from Multispecies Outbreak, Argentina, August 2023

Agustina Rimondi , Ralph E.T. Vanstreels, Valeria Olivera, Agustina Donini, Martina Miqueo Lauriente, and Marcela M. Uhart


We report full-genome characterization of highly pathogenic avian influenza A(H5N1) clade virus from an outbreak among sea lions (August 2023) in Argentina and possible spillover to fur seals and terns. Mammalian adaptation mutations in virus isolated from marine mammals and a human in Chile were detected in mammalian and avian hosts.

In February 2023, the first case of highly pathogenic avian influenza (HPAI) A(H5N1) in Argentina was detected in a wild goose near the border with Bolivia and Chile (Appendix Figure 1) (1). In contrast with Peru and Chile, where extensive mortality of seabirds and marine mammals had been attributed to the virus in the preceding months (2,3), the initial spread of HPAI H5N1 in Argentina was largely limited to backyard and industrial poultry (94 outbreaks), causing the death or disposal of 2.2 million birds. Argentina declared itself free from the disease in poultry on August 8, 2023; before then, HPAI H5N1 detections in wildlife in Argentina had been scarce (7 events during February–April) and limited to aquatic birds (Anatidae, Laridae, and Rallidae) (1,4).
However, soon thereafter, the national animal health services confirmed HPAI H5N1 in South American sea lions (Otaria byronia) from Río Grande, southernmost Argentina. Over subsequent weeks, the virus was detected in sea lions northward along the Argentina coast, and sporadic cases also occurred in South American fur seals (Arctocephalus australis). The most affected site was Punta Bermeja (Appendix Figure 1), the largest sea lion colony in Argentina, where an estimated 811 sea lions died over 2 months; minimal numbers (<5) of fur seals and terns were also affected (1,4).

In collaboration with provincial authorities and park rangers, we collected swab samples (oronasal, rectal, tracheal, lung, and brain) from 16 deceased sea lions, 1 fur seal, 1 great grebe (Podiceps major), and 1 South American tern (Sterna hirundinacea) discovered at Punta Bermeja on August 26, 2023. A sampled adult male sea lion was seen alive showing clinical signs consistent with HPAI infection (inability to stand or walk, muscular tremors and spasms, difficulty breathing, and abundant oral mucus). We tested the samples by real-time reverse transcription PCR targeting influenza A virus (5) and confirmed that all were positive. On the basis of viral RNA yields, we selected brain samples from 4 sea lions, 1 fur seal, and 1 tern for full-genome sequencing (Appendix Figure 2). We used maximum-likelihood tree phylogenetic analysis (6) and mutational analysis to compare the sequences (GenBank accession nos. OR987081–128) with representative HPAI H5N1 strains from South America.

Phylogenetic trees (Figure; Appendix Figure 2) showed that the viruses we identified belong to HPAI H5N1 clade and are closely related to H5N1 viruses that circulated in South America during 2022–2023. Our finding supports the hypothesis that, after introduction from North America into Peru in November 2022, HPAI H5N1 viruses continued spreading across the continent and into Argentina. Of note, the viruses from Punta Bermeja did not cluster with the hemagglutinin and neuraminidase sequences available from HPAI H5N1 first detected in a wild goose in Argentina. Instead, all gene segments from the viruses were closely related to virus sequences from sea lions in Chile and Peru (2; C. Pardo Roa, unpub. data, Link); 6 gene segments (all except polymerase basic protein 1 and nucleocapsid protein) also clustered with the virus isolated from a human in Chile (7). T
hat finding suggests that viruses from Punta Bermeja may have been derived from a separate HPAI H5N1 introduction into Argentina. Because of the lack of genomic data for HPAI H5N1 viruses circulating in Argentina during February–July 2023, the finer scale pathways (local geographic routes and host species involved) of how these viruses arrived at Punta Bermeja remain unclear. Even so, the viruses that we report did not cluster with those from birds in Uruguay, Brazil, or Bird Island (Antarctica), possibly suggesting separate pathways of virus spread.

On the basis of previous comparisons with HPAI H5N1 isolates from other countries in South America, we identified 9 mutations already present in viruses infecting sea lions in Peru and Chile but not in the goose/Guangdong reference strain or in viruses from birds and mammals from North America in 2022 (Table). Specifically, we found Q591K and D701N mutations in polymerase basic 2 associated with increased pathogenicity to mammals (8). The virus we detected in the tern from South America also has those mutations, but they were absent from previously reported HPAI H5N1 viruses from avian hosts in South America (except for A/sanderling/Arica y Parinacota/240265/2023, which has the D701N mutation).
That finding further supports the hypothesis that HPAI H5N1 viruses from sea lions from Peru and Chile acquired mammalian adaptation mutations that improved their ability to infect pinnipeds while possibly retaining the ability to infect avian hosts.
Given the rapid and widespread dissemination of the viruses among pinnipeds in South America and the substantial associated mortalities (3,9), it seems likely that pinniped-to-pinniped transmission played a role in the spread of the mammal-adapted HPAI H5N1 viruses in the region. It is alarming that the HPAI H5N1 viruses infecting pinnipeds and seabirds in Argentina share the same mammalian adaptation mutations as the virus from the affected human in Chile, which highlights the potential threat posed by these viruses to public health.

Dr. Rimondi is a scientist at the National Institute of Agricultural Technology in Argentina and a postdoctoral fellow from Alexander von Humboldt Foundation from Germany working on HPAI H5N1 at the Robert Koch Institute. Her primary research interests focus on molecular epidemiology and host–pathogen interactions of avian influenza viruses.

This isn't the first time that we've seen the possibility of seal-to-seal transmission discussed, but proving it has been difficult.  While not definitive proof, this latest study certainly adds scientific credence to the idea, and reminds us that HPAI H5Nx continues to evolve in the wild. 

While it is still possible there is some species barrier that prevents HPAI H5 from posing a pandemic threat - it continues to expand both its geographic and host range - making it too unpredictable to ignore.