Remember the MINK OUTBREAK in Denmark at the height of COVID-19 pandemic? Bird Flu in mammals (i.e. mink) is extremely dangerous…

The H5N1 mutation (T271A) in the PB2 gene enables transmission

Factsheet on A(H5N1). Highly pathogenic avian influenza virus A(H5N1). “The overall case–fatality ratio (CFR) is around 50% – Source: European Centre for Disease Prevention and Control. An agency of the European Union

  • TRANSMISSION. The incubation period for A(H5N1) infection has been estimated to be up to seven days, although it is usually two to five days after the last known exposure to sick or dead poultry. Longer periods have, however, been suggested [5]. A subset of avian influenza viruses may infect humans; whenever such viruses are circulating in poultry, sporadic infections or small clusters of human cases are possible in people exposed to infected poultry or contaminated environments, especially related to backyard settings. Human infections remain rare, and influenza A(H5N1) viruses do not appear to transmit easily between people. Small clusters with the same exposure prior to disease onset have been observed, yet no sustained human-to-human transmission has been identified. Human cases have reported direct exposure to apparently healthy looking or sick poultry, mostly backyard poultry before onset of disease. The most commonly identified risk factors associated with A(H5N1) virus infection include contact with infected blood/organs or bodily fluids of infected poultry through food preparation practices; touching and caring for infected poultry; exposure to A(H5N1) by swimming or bathing in potentially virus-laden ponds, exposure to A(H5N1) at live bird markets in Asia and via backyard poultry in Egypt [3].

Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022 – Eurosurveillance

This report describes an outbreak of highly pathogenic avian influenza (HPAI) A(H5N1) detected in intensively farmed minks in Europe, which occurred in the Galicia region in northwest Spain in October 2022. We present an in-depth description of the epidemiological, clinical and genetic investigations of this outbreak affecting a single farm and discuss public health implications.

  • DISCUSSION. We present, to the best of our knowledge, the first report of clade HPAI H5N1 virus infection of minks farmed for their fur in Europe. The viruses identified presented the highest similarity with strains of the A/gull/France/22P015977/2022-like genotype, which has already been described in multiple wild bird species and sporadically in poultry across northern Europe [6]. However, the viruses detected at the mink farm are distinguished from all the clade H5N1 viruses characterised thus far in the avian population in Europe as they bear an uncommon mutation (T271A) in the PB2 gene, which may have public health implications. Indeed, the same mutation is present in the avian-like PB2 gene of the 2009 pandemic swine-origin influenza A(H1N1) virus (H1N1pdm). Zhang et al. [9] demonstrated that mutations to the avian virus-conserved residue (threonine, T) reduced polymerase activity and abolished the H1N1pdm virus respiratory droplet transmission in guinea pigs. Furthermore, this study shows that amino acid 271A of PB2 plays a key role in virus acquisition of the mutation at position 226 of HA that confers human receptor recognition. As T271A is an uncommon amino acid change not previously identified among European HPAI H5 viruses in 2020–22, with the exception of a single H5N1 virus from a mammalian host (European polecat), this mutation could have arisen de novo in minks. However, the data available are not sufficient to exclude the possibility of an unobserved circulation of avian viruses bearing this substitution in the avian population. Our findings also indicate that an onward transmission of the virus to other minks may have taken place in the affected farm. This is suggested by the increasing number of infected animals identified after the confirmation of the disease and the progression of the infection from the initially affected area to the entire holding. Additional experimental studies are ongoing to further explore virulence and transmissibility of these viruses. The source of the outbreak remains unknown. No AI cases were reported in poultry farms supplying the poultry by-products. However, considering that the mink spillover event was coincident with a wave of H5N1 virus infections in seabirds in Galicia [4], it can be assumed that wild birds may have played a major role in the virus introduction into the farm. This hypothesis is further supported given that minks were farmed in a partially open building and may have been in contact with wild birds. Indeed, the A/gull/France/22P015977/2022-like genotype has been diagnosed in multiple seabird species across Europe, including common gannets and seagulls, which were the species involved in the H5N1 mortality events registered in Galicia in the weeks before the mink outbreak. Sequencing of the contemporary H5N1 virus-positive wild birds collected in the area will be essential to confirm this assumption. Experimental and field evidence have demonstrated that minks are susceptible and permissive to both avian and human influenza A viruses, leading to the theory that this species could serve as a potential mixing vessel for the interspecies transmission among birds, mammals and human [1014]. In light of this and considering the ongoing HPAI H5N1 panzootic, our findings further highlight the importance of preventing mink infection with such viruses.


  1. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25(3):2000045.  PMID: 31992387 
  2. Spackman E, Senne DA, Myers TJ, Bulaga LL, Garber LP, Perdue ML, et al. Development of a real-time reverse transcriptase PCR assay for type A influenza virus and the avian H5 and H7 hemagglutinin subtypes. J Clin Microbiol. 2002;40(9):325660.  PMID: 12202562 
  3. Hoffmann B, Hoffmann D, Henritzi D, Beer M, Harder TC. Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses. Sci Rep. 2016;6(1):27211.  PMID: 27256976 
  4. Ministry of Agriculture, Fisheries and Food. Consulta de notificación de enfermedades de los animales de declaración obligatoria. [Consultation of notification of animal diseases of obligatory declaration.] Madrid: Spanish Government. [Accessed: 16 Jan 2023]. Spanish. Available from:
  5. European Commission. Commission Implementing Decision (EU) 2021/788 of 12 May 2021 laying down rules for the monitoring and reporting of infections with SARS-CoV-2 in certain animal species. Official Journal of the European Union. Luxembourg: Publications Office of the European Union. 15.5.2021: L173. Available from:
  6. Adlhoch C, Fusaro A, Gonzales JL, Kuiken T, Marangon S, Niqueux É, et al. Avian influenza overview December 2020 – February 2021. EFSA J. 2021;19(3):e06497.  PMID: 33717356 
  7. Bussey KA, Bousse TL, Desmet EA, Kim B, Takimoto T. PB2 residue 271 plays a key role in enhanced polymerase activity of influenza A viruses in mammalian host cells. J Virol. 2010;84(9):4395406.  PMID: 20181719 
  8. Oreshkova N, Molenaar RJ, Vreman S, Harders F, Oude Munnink BB, Hakze-van der Honing RW, et al. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020. Euro Surveill. 2020;25(23):2001005.  PMID: 32553059 
  9. Zhang Y, Zhang Q, Gao Y, He X, Kong H, Jiang Y, et al. Key molecular factors in hemagglutinin and PB2 contribute to efficient transmission of the 2009 H1N1 pandemic influenza virus. J Virol. 2012;86(18):966674.  PMID: 22740390 
  10. Sun H, Li F, Liu Q, Du J, Liu L, Sun H, et al. Mink is a highly susceptible host species to circulating human and avian influenza viruses. Emerg Microbes Infect. 2021;10(1):47280.  PMID: 33657971 
  11. Peng L, Chen C, Kai-yi H, Feng-xia Z, Yan-li Z, Zong-shuai L, et al. Molecular characterization of H9N2 influenza virus isolated from mink and its pathogenesis in mink. Vet Microbiol. 2015;176(1-2):8896.  PMID: 25655813 
  12. Liu J, Li Z, Cui Y, Yang H, Shan H, Zhang C. Emergence of an Eurasian avian-like swine influenza A (H1N1) virus from mink in China. Vet Microbiol. 2020;240:108509.  PMID: 31902506 
  13. Gagnon CA, Spearman G, Hamel A, Godson DL, Fortin A, Fontaine G, et al. Characterization of a Canadian mink H3N2 influenza A virus isolate genetically related to triple reassortant swine influenza virus. J Clin Microbiol. 2009;47(3):7969.  PMID: 19116358 
  14. Kiss I, Gyarmati P, Zohari S, Ramsay KW, Metreveli G, Weiss E, et al. Molecular characterization of highly pathogenic H5N1 avian influenza viruses isolated in Sweden in 2006. Virol J. 2008;5(1):113.  PMID: 18837987 
  15. Fenollar F, Mediannikov O, Maurin M, Devaux C, Colson P, Levasseur A, et al. Mink, SARS-CoV-2, and the human-animal interface. Front Microbiol. 2021;12:663815.  PMID: 33868218 
  16. He G, Qiao J, Dong C, He C, Zhao L, Tian Y. Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China. Antiviral Res. 2008;77(1):726.  PMID: 17897729 
  17. Bandelt H-J, Forster P, Röhl A. Median-joining networks for inferring intraspecific phylogenies. Mol Biol Evol. 1999;16(1):3748.  PMID: 10331250 

Learn More

  • Researchers detail H5N1 avian flu outbreak at mink farm in Spain – CIDRAP. 20 JAN 2023
  • Bird Flu – NHS
    • Bird flu, or avian flu, is an infectious type of influenza that spreads among birds. In rare cases, it can affect humans. There are lots of different strains of bird flu virus. Most of them don’t infect humans. But there are 4 strains that have caused concern in recent years: H5N1 (since 1997) H7N9 (since 2013) H5N6 (since 2014) H5N8 (since 2016). Although H5N1, H7N9 and H5N6 don’t infect people easily and aren’t usually spread from human to human, several people have been infected around the world, leading to a number of deaths. In February 2021 H5N8 was found to have infected a small number of people for the first time, in Russia.
  • New bird flu pandemic fears as top virologists sound alarm over ‘worrisome’ spread of killer virus in mink – and say it raises chilling prospect that H5N1 could jump to humans and sweep planet – DAILY MAIL. 20 JAN 2023
    • Top virologists alarmed after bird flu strain H5N1 spreads between mammals. Outbreak occurred in a farm in Spain in October which housed 52,000 mink. It raises prospect it could acquire mutations to spread easier among humans. Professor Rupert Beale, an immunology expert at the world-renowned Francis Crick Institute in London, said: ‘We should have vaccine contingency plans already.’ And Professor Isabella Eckerle, a virologist at the University of Geneva’s Centre for Emerging Viral Diseases, called the findings ‘really worrisome’. Other experts warned that outbreaks among mink could lead to a recombination event — when two viruses switch genetic material to make a new hybrid. A similar process is thought to have caused the global 2009 swine flu crisis that infected millions across the planet. The same biological phenomenon was also seen during the Covid pandemic, such as so-called Deltacron — a recombination of Delta and Omicron, first detected in France last February. For decades, scientists have warned that bird flu is the most likely contender for triggering the next pandemic. Experts say this is because of the threat of recombination — with high levels of human flu strains raising the risk of a human becoming co-infected with avian flu as well. This could see a deadly strain of bird flu merge with a transmissible seasonal flu. The mink outbreak occurred in a farm in Galicia, north west Spain, in October which housed 52,000 of the animals. It was only spotted after a sudden surge in the animals dying. Up to four per cent died in one week during the course of the outbreak, which was declared over by mid-November. Farm vets swabbed the minks and the samples were analysed at a Government lab, where they tested positive for H5N1. It led to all of the animals being culled, farm workers isolating for 10 days and heightened security measures in farms across the country.
Go to Top