Cross-species and mammal-to-mammal transmission of clade 2.3.4.4b highly pathogenic avian influenza A/H5N1 with PB2 adaptations

Catalina Pardo-Roa, Martha I. Nelson, Naomi Ariyama, Carolina Aguayo, Leonardo I. Almonacid, Ana S. Gonzalez-Reiche, Gabriela Muñoz, Mauricio Ulloa, Claudia Ávila, Carlos Navarro, Rodolfo Reyes, Pablo N. Castillo-Torres, Christian Mathieu, Ricardo Vergara, Álvaro González, Carmen Gloria González, Hugo Araya, Andrés Castillo, Juan Carlos Torres, Paulo Covarrubias, Patricia Bustos, Harm Bakel, Jorge Fernández, Rodrigo A. Fasce, Magdalena Johow (), Víctor Neira () and Rafael A. Medina ()
Additional contact information
Catalina Pardo-Roa: Pontificia Universidad Católica de Chile
Martha I. Nelson: National Institutes of Health
Naomi Ariyama: Emory Center of Excellence of Influenza Research and Response (Emory-CEIRR)
Carolina Aguayo: Servicio Agrícola y Ganadero (SAG)
Leonardo I. Almonacid: Pontificia Universidad Católica de Chile
Ana S. Gonzalez-Reiche: on Influenza Pathogenesis and Transmission (CRIPT) Center of Excellence of Influenza Research and Response (CEIRR)
Gabriela Muñoz: Universidad de Chile
Mauricio Ulloa: Servicio Nacional de Pesca y Acuicultura (SERNAPESCA)
Claudia Ávila: Servicio Agrícola y Ganadero (SAG)
Carlos Navarro: Servicio Nacional de Pesca y Acuicultura (SERNAPESCA)
Rodolfo Reyes: Servicio Nacional de Pesca y Acuicultura (SERNAPESCA)
Pablo N. Castillo-Torres: Pontificia Universidad Católica de Chile
Christian Mathieu: Servicio Agrícola y Ganadero (SAG)
Ricardo Vergara: Servicio Agrícola y Ganadero (SAG)
Álvaro González: Servicio Agrícola y Ganadero (SAG)
Carmen Gloria González: Servicio Agrícola y Ganadero (SAG)
Hugo Araya: Servicio Agrícola y Ganadero (SAG)
Andrés Castillo: Public Health Institute of Chile
Juan Carlos Torres: Servicio Agrícola y Ganadero (SAG)
Paulo Covarrubias: Public Health Institute of Chile
Patricia Bustos: Public Health Institute of Chile
Harm Bakel: on Influenza Pathogenesis and Transmission (CRIPT) Center of Excellence of Influenza Research and Response (CEIRR)
Jorge Fernández: Public Health Institute of Chile
Rodrigo A. Fasce: Public Health Institute of Chile
Magdalena Johow: Servicio Agrícola y Ganadero (SAG)
Víctor Neira: Emory Center of Excellence of Influenza Research and Response (Emory-CEIRR)
Rafael A. Medina: Pontificia Universidad Católica de Chile

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Highly pathogenic H5N1 avian influenza viruses (HPAIV) belonging to lineage 2.3.4.4b emerged in Chile in December 2022, leading to mass mortality events in wild birds, poultry, and marine mammals and one human case. We detected HPAIV in 7,33% (714/9745) of cases between December 2022–April 2023 and sequenced 177 H5N1 virus genomes from poultry, marine mammals, a human, and wild birds spanning >3800 km of Chilean coastline. Chilean viruses were closely related to Peru’s H5N1 outbreak, consistent with north-to-south spread down the Pacific coastline. One human virus and nine marine mammal viruses in Chile had the rare PB2 D701N mammalian-adaptation mutation and clustered phylogenetically despite being sampled 5 weeks and hundreds of kilometers apart. These viruses shared additional genetic signatures, including another mammalian PB2 adaptation (Q591K, n = 6), synonymous mutations, and minor variants. Several mutations were detected months later in sealions in the Atlantic coast, indicating that the pinniped outbreaks on the west and east coasts of South America are genetically linked. These data support sustained mammal-to-mammal transmission of HPAIV in marine mammals over thousands of kilometers of Chile’s Pacific coastline, which subsequently continued through the Atlantic coastline.

Date: 2025
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DOI: 10.1038/s41467-025-57338-z

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