Literature detail

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^1,2,3 Martha I Nelson^4,5 Naomi Ariyama^3,6 Carolina Aguayo⁷ Leonardo I Almonacid^8,9 Ana S Gonzalez-Reiche^5,10 Gabriela Muñoz⁶ Mauricio Ulloa^11,12 Claudia Ávila⁷ Carlos Navarro¹¹ Rodolfo Reyes¹¹ Pablo N Castillo-Torres^2,3 Christian Mathieu⁷ Ricardo Vergara⁷ Álvaro González⁷ Carmen Gloria González⁷ Hugo Araya⁷ Andrés Castillo¹³ Juan Carlos Torres⁷ Paulo Covarrubias¹³ Patricia Bustos¹⁴ Harm van Bakel^5,10,15 Jorge Fernández¹³ Rodrigo A Fasce¹⁴ Magdalena Johow¹⁶ Víctor Neira^17,18,19 Rafael A Medina^20,21,22,23

Affiliations 23 institutions

Department of Child and Adolescent Health, School of Nursing, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
Emory Center of Excellence of Influenza Research and Response (Emory-CEIRR), Atlanta, GA, USA.
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
Center for Research, on Influenza Pathogenesis and Transmission (CRIPT) Center of Excellence of Influenza Research and Response (CEIRR), New York, NY, USA.
Departamento de Medicina Preventiva Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile.
Servicio Agrícola y Ganadero (SAG), Santiago, Chile.
Molecular Bioinformatics Laboratory, Department of Molecular Genetics and Microbiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Servicio Nacional de Pesca y Acuicultura (SERNAPESCA), Santiago, Chile.
Veterinary Histology and Pathology, Institute of Animal Health and Food Safety, Veterinary School, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Molecular Genetic Subdepartment, Public Health Institute of Chile, Santiago, Chile.
Section of Respiratory and Exanthematic Viruses, Public Health Institute of Chile, Santiago, Chile.
Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Servicio Agrícola y Ganadero (SAG), Santiago, Chile. [email protected].
Emory Center of Excellence of Influenza Research and Response (Emory-CEIRR), Atlanta, GA, USA. [email protected].
Center for Research, on Influenza Pathogenesis and Transmission (CRIPT) Center of Excellence of Influenza Research and Response (CEIRR), New York, NY, USA. [email protected].
Departamento de Medicina Preventiva Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile. [email protected].
Department of Pediatric Infectious Diseases and Immunology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. [email protected].
Emory Center of Excellence of Influenza Research and Response (Emory-CEIRR), Atlanta, GA, USA. [email protected].
Center for Research, on Influenza Pathogenesis and Transmission (CRIPT) Center of Excellence of Influenza Research and Response (CEIRR), New York, NY, USA. [email protected].
Department of Pathology and Laboratory Medicine, School of Medicine, Emory Vaccine Center, Emory University, Atlanta, GA, USA. [email protected].

PMID 40044729 2025 Nat Commun eng epublish

PubMed DOI Browse context

Article

Publication summary

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.

Influenza A Virus, H5N1 Subtype Influenza in Birds Influenza, Human Mammals Orthomyxoviridae Infections RNA-Dependent RNA Polymerase Viral Proteins Adaptation, Physiological Animals Animals, Wild Birds Chile Disease Outbreaks Genome, Viral Humans Mutation Phylogeny Poultry

Structured evidence records

Evidence records

13 total

Outbreak Investigation 4 records

Outbreak Investigation Extraction confidence 0.95

Key finding

Outbreaks of HPAIV H5N1 occurred in wild birds, poultry, marine mammals, and one human in Chile starting December 2022.

Virus

Host

Location

Supporting text

Transmission direction: unknown
Geographic raw: Chile
Country inferred: Chile
Outbreak time: December 2022
Outbreak scale: mass mortality events

Outbreak Investigation Extraction confidence 0.95

Key finding

Outbreaks of HPAIV H5N1 occurred in poultry in Chile starting December 2022.

Virus

Host

Location

Supporting text

Transmission direction: unknown
Geographic raw: Chile
Country inferred: Chile
Outbreak time: December 2022
Outbreak scale: mass mortality events

Outbreak Investigation Extraction confidence 0.95

Key finding

Outbreaks of HPAIV H5N1 occurred in marine mammals in Chile starting December 2022.

Virus

Host

Location

Supporting text

Transmission direction: animal-to-animal
Geographic raw: Chile
Country inferred: Chile
Outbreak time: December 2022
Outbreak scale: mass mortality events

Outbreak Investigation Extraction confidence 0.90

Key finding

Sustained mammal-to-mammal transmission of H5N1 in marine mammals occurred in Chile.

Virus

Host

Location

Supporting text

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.

Method: sequencing
Transmission direction: animal-to-animal
Geographic raw: Chile
Country inferred: Chile
Outbreak time: December 2022-April 2023

Zoonotic Surveillance 3 records

Zoonotic Surveillance Extraction confidence 0.95

Key finding

Genomic surveillance detected and sequenced highly pathogenic avian influenza H5N1 genomes from poultry, wild birds, marine mammals, and a human across coastal Chile.

Virus

Host

Location

Supporting text

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.

Method: genomic sequencing
Geographic raw: Chilean coastline
Country inferred: Chile

Zoonotic Surveillance Extraction confidence 0.95

Key finding

Genomic surveillance detected and sequenced highly pathogenic avian influenza H5N1 genomes from poultry along the Chilean coastline.

Virus

Host

Location

Supporting text

Method: genomic sequencing
Geographic raw: Chilean coastline
Country inferred: Chile

Zoonotic Surveillance Extraction confidence 0.95

Key finding

Genomic surveillance detected and sequenced highly pathogenic avian influenza H5N1 genomes from marine mammals along the Chilean coastline.

Virus

Host

Location

Supporting text

Method: genomic sequencing
Geographic raw: Chilean coastline
Country inferred: Chile

Genomic Evolution 2 records

Genomic Evolution Extraction confidence 0.90

Key finding

Chilean H5N1 viruses from a human and marine mammals shared PB2 D701N and Q591K mammalian-adaptation mutations and phylogenetically clustered, indicating evolution toward mammalian adaptation and sustained transmission.

Virus

Host

Location

Supporting text

We sequenced 177 H5N1 virus genomes from poultry, marine mammals, a human, and wild birds spanning >3800 km of Chilean 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.

Genes or proteins: PB2
Analysis methods: whole genome sequencing; phylogenetic analysis

Genomic Evolution Extraction confidence 0.90

Key finding

Phylogenetic evidence showed Chilean H5N1 viruses closely related to Peruvian H5N1 viruses, demonstrating southward lineage spread along the Pacific coast.

Virus

Host

Location

Supporting text

Chilean viruses were closely related to Peru's H5N1 outbreak, consistent with north-to-south spread down the Pacific coastline.

Genes or proteins: whole genome
Analysis methods: phylogenetic analysis

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.95

Key finding

H5N1 viruses from humans and marine mammals in Chile contained the PB2 D701N mutation conferring mammalian adaptation, suggesting molecular adaptation linked to cross-species and mammal-to-mammal transmission.

Virus

Host

Location

Supporting text

Genes or proteins: PB2
Mutations: D701N
Mechanism types: polymerase_activity; mammalian_adaptation

Molecular Adaptation Extraction confidence 0.90

Key finding

Chilean H5N1 viruses also carried the PB2 Q591K mutation associated with mammalian adaptation, highlighting molecular changes enhancing replication or host adaptation in mammals.

Virus

Host

Location

Supporting text

These viruses shared additional genetic signatures, including another mammalian PB2 adaptation (Q591K, n = 6), synonymous mutations, and minor variants.

Genes or proteins: PB2
Mutations: Q591K
Mechanism types: polymerase_activity; mammalian_adaptation

Cross Species Transmission 1 records

Cross Species Transmission Extraction confidence 0.98

Key finding

Highly pathogenic avian influenza A/H5N1 was transmitted between marine mammals, indicating sustained mammal-to-mammal spread along the Chilean and Atlantic coasts of South America.

Virus

Host

Location

Supporting text

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.

Method: sequencing; phylogenetic analysis
Study design: phylogenetic analysis
Transmission direction: animal-to-animal
Geographic raw: Chile's Pacific coastline
Country inferred: Chile

Spillover Event 1 records

Spillover Event Extraction confidence 0.95

Key finding

An avian-origin H5N1 virus infected a human in Chile, directly indicating animal-to-human transmission of clade 2.3.4.4b HPAIV.

Virus

Host

Location

Supporting text

Method: sequencing; phylogenetic analysis
Study design: outbreak investigation
Transmission direction: animal-to-human
Geographic raw: Chile
Country inferred: Chile

Citation context

References

72 references

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Evidence overview

Evidence 13

Types 6

Virus 1

Host 3

Evidence types

Outbreak Investigation 4 Zoonotic Surveillance 3 Genomic Evolution 2 Molecular Adaptation 2 Cross Species Transmission 1 Spillover Event 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Nature communications
Volume / Issue / Pages: 16 / 1 / 2232
ISSN: 2041-1723
Journal country: England
DOI: 10.1038/s41467-025-57338-z