OmniVira

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].
PMID38750016 DOI10.1038/s41467-024-48475-y Year2024 Journal Nature communications Nat Commun Languageeng Statusepublish

Abstract

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.

Supporting text Virus Host Location
Ferrets 79 Influenza A Virus, H5N1 Subtype 300 Mink 48 Orthomyxoviridae Infections 228 Animals 1948 Disease Outbreaks 170 Female 289 Humans 1440 Influenza, Human 286 Male 224 Mutation 209 Risk Assessment 13 Viral Proteins 152

Evidence records

4 total
Experimental Infection
3 records · 2 evidence types
Evidence type Pathogenicity Experiment
1 records
OVE8053 Pathogenicity Experiment
Key finding

A mink-derived H5N1 virus exhibited low infectious dose and remained virulent in ferrets at low doses.

Virus
Influenza A virus H5N1
Host
domestic ferret Mustela putorius furo Experimental system
Location
Not specified
Supporting text

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. The H5N1 virus also has a low infectious dose and remains virulent at low doses.

Method
controlled dose infection experiment | clinical observation of virulence or disease severity in ferrets
Experimental system
ferret infection model
Evidence type Experimental Transmission
2 records
OVE8051 Experimental Transmission
Key finding

An H5N1 isolate derived from mink transmitted by direct contact to 75% of exposed ferrets in controlled infection experiments.

Virus
Influenza A virus H5N1
Host
domestic ferret Mustela putorius furo Experimental system American mink Neogale vison Experimental system
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.

Method
ferret model | controlled contact transmission experiment
Experimental system
ferret contact transmission model
OVE8052 Experimental Transmission
Key finding

An H5N1 isolate derived from mink transmitted by airborne exposure to 37.5% of contact ferrets in controlled experiments.

Virus
Influenza A virus H5N1
Host
domestic ferret Mustela putorius furo Experimental system American mink Neogale vison Experimental system
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
airborne transmission study | ferret model
Experimental system
ferret airborne transmission model
Functional Mechanism
1 records · 1 evidence types
Evidence type Molecular Adaptation
1 records
OVE8054 Molecular Adaptation
Key finding

The H5N1 isolate derived from mink carries an adaptive PB2 T271A mutation whose reversal reduces mortality and airborne transmission, indicating molecular adaptation related to virulence and transmissibility.

Virus
Influenza A virus H5N1
Host
Not specified
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. 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
virulence adaptation | transmission fitness