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Literature detail

Risk assessment of a highly pathogenic H5N1 influenza virus from mink.

Katherine H Restori1,2 Kayla M Septer1,3 Cassandra J Field1,2,3 Devanshi R Patel1,3 David VanInsberghe4,5 Vedhika Raghunathan4,5 Anice C Lowen4,5 Troy C Sutton6,7,8
Affiliations 8 institutions
  1. Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA, USA.
  2. Emory Center of Excellence of Influenza Research and Response (CEIRR), University Park, PA, USA.
  3. The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, USA.
  4. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
  5. Emory Center of Excellence of Influenza Research and Response (CEIRR), Atlanta, GA, USA.
  6. Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA, USA. [email protected].
  7. Emory Center of Excellence of Influenza Research and Response (CEIRR), University Park, PA, USA. [email protected].
  8. The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, USA. [email protected].
PMID 38750016 2024 Nat Commun eng epublish
PubMed DOI Browse context

Article

Publication summary

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat. To assess this threat, using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts. Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses. This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission. This is the first report of a H5N1 clade 2.3.4.4b virus exhibiting direct contact and airborne transmissibility in ferrets. These data indicate heightened pandemic potential of the panzootic H5N1 viruses and emphasize the need for continued efforts to control outbreaks and monitor viral evolution.

Ferrets Influenza A Virus, H5N1 Subtype Mink Orthomyxoviridae Infections Animals Disease Outbreaks Female Humans Influenza, Human Male Mutation Risk Assessment Viral Proteins

Structured evidence records

Evidence records

5 total
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

An H5N1 virus originating from mink transmitted by direct contact and through the air to ferrets.

Virus
IAV H5N1
Location
Not specified
Supporting text

Using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts.

Method
direct contact transmission study; airborne transmission study
Study design
animal experiment
Transmission direction
animal-to-animal
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.70
Key finding

Genome sequencing of the H5N1 clade 2.3.4.4b isolate from mink revealed an adaptive PB2 T271A mutation whose reversion decreased mortality and airborne spread in ferrets.

Virus
IAV H5N1
Location
Not specified
Supporting text

Sequence analyses show no mutations were associated with transmission. The H5N1 virus also has a low infectious dose and remains virulent at low doses. This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission.

Genes or proteins
PB2
Analysis methods
sequence analysis
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.95
Key finding

A mink-derived H5N1 clade 2.3.4.4b virus experimentally infected ferrets, transmitting efficiently by direct contact and partially by airborne exposure.

Virus
IAV H5N1
Location
Not specified
Supporting text

Using the ferret model, we show an H5N1 isolate derived from mink transmits by direct contact to 75% of exposed ferrets and, in airborne transmission studies, the virus transmits to 37.5% of contacts.

Method
transmission study; experimental infection
Experimental system
in vivo animal experiment
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

The mink-derived H5N1 clade 2.3.4.4b virus carries the adaptive PB2 T271A mutation that increases virulence and transmissibility, and reversing it decreases these effects.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

This isolate carries the adaptive mutation, PB2 T271A, and reversing this mutation reduces mortality and airborne transmission.

Genes or proteins
PB2
Mutations
PB2 T271A
Mechanism types
polymerase_activity; transmission_fitness; pathogenicity
Outbreak Investigation 1 records
Outbreak Investigation Extraction confidence 0.75
Key finding

Highly pathogenic H5N1 clade 2.3.4.4b viruses caused outbreaks in farmed mink and seals.

Virus
IAV H5N1
Location
Not specified
Supporting text

Outbreaks of highly pathogenic H5N1 clade 2.3.4.4b viruses in farmed mink and seals combined with isolated human infections suggest these viruses pose a pandemic threat.

Transmission direction
animal-to-animal
Outbreak setting
farm