OmniVira

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.
PMID40872303 DOI10.3390/pathogens14080793 Year2025 Journal Pathogens (Basel, Switzerland) Pathogens Languageeng Statusepublish

Abstract

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 (Thalasseus maximus) 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.

Supporting text Virus Host Location
avian influenza 57 genetic clades 1 mammal hosts 1 phylogeography 35 South America 8 transmission routes 1 Influenza A Virus, H5N1 Subtype 300 Influenza in Birds 341 Animals 1948 Birds 212 Disease Outbreaks 170 Genome, Viral 317 Humans 1440 Phylogeny 805 Phylogeography 30 South America 2 Uruguay 4

Evidence records

5 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type Viral Detection
1 records
OVE9755 Viral Detection
Key finding

A viral genome of highly pathogenic avian influenza H5N1 clade 2.3.4.4b was detected and sequenced from a royal tern in Uruguay during the 2023 outbreaks.

Virus
Influenza A virus H5N1
Host
royal tern Thalasseus maximus Natural host
Location
Uruguay
Supporting text

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 (Thalasseus maximus) collected at the end of the outbreaks.

Method
viral genome sequencing
Sample type
royal tern sample
Geographic raw
Uruguay
Country inferred
URY
Functional Mechanism
1 records · 1 evidence types
Evidence type Molecular Adaptation
1 records
OVE9757 Molecular Adaptation
Key finding

H5N1 viruses associated with marine mammals in Uruguay display adaptive residues in the PB2 protein, suggesting molecular adaptation to marine mammal hosts.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
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. 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.

Genes or proteins
PB2
Mechanism types
replication adaptation | host-range expansion
Genomic Evolution
3 records · 1 evidence types
Evidence type Phylogenetic Evolution
3 records
OVE9756 Phylogenetic Evolution
Key finding

Phylogeographic reconstruction identified two distinct South American phylogroups of H5N1 clade 2.3.4.4b involving Uruguayan strains, one associated with wild birds and poultry and another linked to marine mammals.

Virus
Influenza A virus H5N1
Host
birds Aves Natural host mammals Mammalia Natural host
Location
Not specified
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.

Genes or proteins
PB2 protein
Analysis methods
phylogeographic reconstruction | phylogenetic analysis
OVE9758 Phylogenetic Evolution
Key finding

Phylogeographic analysis identified an avian-derived H5N1 transmission pathway from Argentina to Uruguay, indicating animal-to-animal spread via avian hosts.

Virus
Influenza A virus H5N1
Host
birds Aves Natural host
Location
Argentina 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. 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.

Analysis methods
phylogenetic reconstruction | genome sequencing
OVE9759 Phylogenetic Evolution
Key finding

The study inferred a pinniped-derived H5N1 transmission route from Chile to Uruguay, indicating cross-species spread involving marine mammals.

Virus
Influenza A virus H5N1
Host
pinnipeds Pinnipedia Natural host birds Aves Natural host
Location
Chile 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. 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.

Analysis methods
phylogenetic reconstruction | genome sequencing