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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Risk assessment of a highly pathogenic H5N1 influenza virus from mink
Katherine H Restori1,2, Kayla M Septer1,3, Cassandra J Field1,2,3
1Department of Veterinary and Biomedical Science, The Pennsylvania State University, University Park, PA, USA.
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.
Insights
Highly pathogenic H5N1 avian influenza viruses from mink are transmissible between ferrets via direct contact and airborne routes. This finding highlights the urgent need for enhanced surveillance and control of H5N1 outbreaks due to pandemic potential.
Area of Science:
- Virology
- Epidemiology
- One Health
Background:
- Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses have caused widespread outbreaks in farmed animals, including mink and seals.
- Isolated human infections with H5N1 raise concerns about potential zoonotic transmission and pandemic threat.
Purpose of the Study:
- To evaluate the transmission dynamics and virulence of a mink-derived H5N1 clade 2.3.4.4b virus in a mammalian model.
- To assess the pandemic potential of current H5N1 strains.
Main Methods:
- Ferrets were used as a model to study direct contact and airborne transmission of an H5N1 isolate from mink.
- Sequence analysis was performed to identify mutations associated with transmission.
- Virulence and infectious dose were assessed at low viral doses.
Main Results:
- The H5N1 mink isolate transmitted via direct contact to 75% of exposed ferrets and via airborne routes to 37.5% of contacts.
- No specific mutations were identified as solely responsible for transmission.
- The virus demonstrated a low infectious dose and maintained virulence at low doses.
- A specific adaptive mutation (PB2 T271A) was present, and its reversal reduced mortality and airborne transmission.
Conclusions:
- This is the first report of H5N1 clade 2.3.4.4b virus exhibiting both direct contact and airborne transmissibility in ferrets.
- The findings indicate a heightened pandemic potential for the currently circulating H5N1 viruses.
- Continued efforts in outbreak control and viral evolution monitoring are crucial.

