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Converging Transmission Routes of the Highly Pathogenic Avian Influenza H5N1 Clade 2.3.4.4b Virus in Uruguay: Phylogeographic Insights into Its Spread Across South America.

Ana Marandino1 Gonzalo Tomás1 Yanina Panzera1 Joaquín Williman1 Filipe Zimmer Dezordi2 Gabriel Luz Wallau2,3 Sirley Rodríguez4 Ramiro Pérez4 Lucía Bassetti4 Raúl Negro4 Valeria Uriarte5 Carmen Leizagoyen5 Ruben Pérez1
Affiliations 5 institutions
  1. Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay.
  2. Instituto Aggeu Magalhães (IAM)-Fundação Oswaldo Cruz (FIOCRUZ), Recife 50670-420, Brazil.
  3. Bernhard Nocht Institute for Tropical Medicine, National Reference Center for Tropical Infectious Diseases, WHO Collaborating Center for Arbovirus and Hemorrhagic Fever Reference and Research, D-20359 Hamburg, Germany.
  4. División de Laboratorios Veterinarios "Miguel C. Rubino", Dirección General de Servicios Ganaderos, Ministerio de Ganadería, Agriculturay Pesca, Montevideo 12100, Uruguay.
  5. Dirección Nacional de Biodiversidad y Servicios Ecosistémicos (DINABISE), Ministerio de Ambiente, Montevideo 11100, Uruguay.
PMID 40872303 2025 Pathogens eng epublish
PubMed DOI Browse context

Article

Publication summary

The highly pathogenic avian influenza H5N1 2.3.4.4b clade virus has caused widespread outbreaks across South America, primarily affecting seabirds, poultry, and marine mammals. The virus likely reached the continent through migratory birds from North America, initially spreading along the Pacific coast before advancing into Atlantic-bordering countries such as Argentina, Uruguay, and Brazil. This study investigated the dynamics of H5N1 strains in Uruguay during outbreaks from February and October 2023. We analyzed an updated South American database, including a newly sequenced viral genome from a royal tern (<i>Thalasseus maximus</i>) collected at the end of the outbreaks. Phylogeographic reconstruction revealed two distinct South American phylogroups comprising Uruguayan strains: one mainly driven by wild birds and poultry, with the royal tern strain clustering with Brazilian isolates, and another primarily associated with marine mammals, displaying adaptive residues in the PB2 protein. In Uruguay, these phylogroups delineate two main transmission routes: (i) an avian-derived pathway originating in Argentina and (ii) a pinniped-derived route from Chile. Brazil, initially colonized via the Argentine route, later emerged as a secondary source for Uruguay. This host-pathway interplay underscores the virus's cross-species potential and highlights the need for coordinated regional surveillance within a One Health framework to mitigate zoonotic risks.

avian influenza genetic clades mammal hosts phylogeography South America transmission routes Influenza A Virus, H5N1 Subtype Influenza in Birds Animals Birds Disease Outbreaks Genome, Viral Humans Phylogeny Phylogeography South America Uruguay

Structured evidence records

Evidence records

8 total
Outbreak Investigation 3 records
Outbreak Investigation Extraction confidence 0.70
Key finding

Outbreaks of H5N1 clade 2.3.4.4b occurred in Uruguay during February–October 2023, affecting seabirds, poultry, and marine mammals; phylogeographic analysis linked avian and pinniped transmission routes originating from Argentina and Chile.

Virus
IAV H5N1
Host
Aves Metazoa
Location
Uruguay Uruguay
Supporting text

The highly pathogenic avian influenza H5N1 2.3.4.4b clade virus has caused widespread outbreaks across South America, primarily affecting seabirds, poultry, and marine mammals. This study investigated the dynamics of H5N1 strains in Uruguay during outbreaks from February and October 2023.

Method
phylogeographic reconstruction; genome sequencing
Transmission direction
animal-to-animal
Geographic raw
Uruguay
Country inferred
Uruguay
Outbreak time
February and October 2023
Outbreak Investigation Extraction confidence 0.70
Key finding

Two outbreak-associated phylogroups of H5N1 were identified in Uruguay, one involving wild birds and poultry, and another involving marine mammals.

Virus
IAV H5N1
Host
Aves Aves
Location
Uruguay Uruguay
Supporting text

Phylogeographic reconstruction revealed two distinct South American phylogroups comprising Uruguayan strains: one mainly driven by wild birds and poultry, and another primarily associated with marine mammals.

Method
phylogeographic reconstruction
Transmission direction
animal-to-animal
Geographic raw
Uruguay
Country inferred
Uruguay
Outbreak time
February and October 2023
Outbreak Investigation Extraction confidence 0.70
Key finding

A distinct marine mammal-associated phylogroup of H5N1 was detected in Uruguay, consistent with a pinniped-derived transmission route from Chile.

Virus
IAV H5N1
Location
Uruguay Uruguay
Supporting text

Another phylogroup was primarily associated with marine mammals, displaying adaptive residues in the PB2 protein. In Uruguay, these phylogroups delineate two main transmission routes: (i) an avian-derived pathway originating in Argentina and (ii) a pinniped-derived route from Chile.

Method
phylogeographic reconstruction; genome sequencing
Transmission direction
animal-to-animal
Geographic raw
Uruguay
Country inferred
Uruguay
Outbreak time
February and October 2023
Cross Species Transmission 2 records
Cross Species Transmission Extraction confidence 0.95
Key finding

H5N1 2.3.4.4b viruses in Uruguay showed evidence of transmission between wild birds and poultry.

Virus
IAV H5N1
Host
Aves Aves
Location
Uruguay Uruguay
Supporting text

Phylogeographic reconstruction revealed two distinct South American phylogroups comprising Uruguayan strains: one mainly driven by wild birds and poultry, with the royal tern strain clustering with Brazilian isolates, and another primarily associated with marine mammals, displaying adaptive residues in the PB2 protein.

Method
sequencing; phylogeographic reconstruction
Study design
phylogeographic analysis
Transmission direction
animal-to-animal
Geographic raw
Uruguay
Country inferred
Uruguay
Cross Species Transmission Extraction confidence 0.95
Key finding

H5N1 2.3.4.4b viruses in Uruguay showed evidence of a marine mammal (pinniped)-derived transmission route.

Virus
IAV H5N1
Location
Uruguay Uruguay
Supporting text

In Uruguay, these phylogroups delineate two main transmission routes: (i) an avian-derived pathway originating in Argentina and (ii) a pinniped-derived route from Chile.

Method
sequencing; phylogeographic reconstruction
Study design
phylogeographic analysis
Transmission direction
animal-to-animal
Geographic raw
Uruguay
Country inferred
Uruguay
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.90
Key finding

Phylogeographic and phylogenetic analyses of a new H5N1 2.3.4.4b genome from a royal tern in Uruguay identified two distinct phylogroups with PB2 adaptive residues linked to avian and marine mammal hosts.

Virus
IAV H5N1
Location
Not specified
Supporting text

We analyzed an updated South American database, including a newly sequenced viral genome from a royal tern (Thalasseus maximus)... Phylogeographic reconstruction revealed two distinct South American phylogroups comprising Uruguayan strains... displaying adaptive residues in the PB2 protein.

Genes or proteins
PB2
Analysis methods
phylogeographic reconstruction; phylogenetic analysis; genome sequencing
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.80
Key finding

H5N1 clade 2.3.4.4b strains linked to marine mammals in Uruguay possess adaptive residues in PB2, suggesting host-specific molecular adaptation.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

Another phylogroup primarily associated with marine mammals displayed adaptive residues in the PB2 protein.

Genes or proteins
PB2
Mechanism types
polymerase_activity; host_factor_interaction
Zoonotic Surveillance 1 records
Zoonotic Surveillance Extraction confidence 0.90
Key finding

A royal tern from Uruguay was sampled and its H5N1 genome sequenced as part of phylogeographic surveillance of avian influenza virus spread across South America.

Virus
IAV H5N1
Location
Uruguay Uruguay
Supporting text

We analyzed an updated South American database, including a newly sequenced viral genome from a royal tern (Thalasseus maximus) collected at the end of the outbreaks.

Method
genome sequencing; phylogeography
Geographic raw
Uruguay
Country inferred
Uruguay