Last October we saw the initial outbreak report from Spain: Avian H5N1 Spillover Into Farmed Mink, and reviewed the rather extensive history of farmed mink being susceptible to human and avian flu, along with SARS-CoV-2.
Mink are a member of the Mustelidae family of carnivorous mammals, which also includes otters, badgers, weasel, martens, ferrets, and wolverines. Many of these species are susceptible to flu viruses – most notably ferrets – which are often used in influenza research.
Spillovers into farmed animals are considered particularly worrisome, because they allow for serial transmission across a large number of hosts, which may result in host adaptation.
That pretty much described what occurred in the fall of 2020, when we saw several new strains of COVID emerge from infected farm-raised mink, and go on to infect humans in the community (see Denmark Orders Culling Of All Mink Following Discovery Of Mutated Coronavirus).
When H5N1 was reported in the Mink farm last October, there had only been 3 known human infections with the 220.127.116.11b clade of the virus (1 UK, 1 US, 1 in Spain), and all had been either very mild or asymptomatic.
Since then, we've learned of three severe cases, including 1 fatality, which raises the stakes considerably.
Today the journal Eurosurveillance provides a detailed report on the outbreak in mink, including the detection of rare mutation (T271A), which `enhances the polymerase activity of influenza A viruses in mammalian host cells and mice'.
I've only posted some excerpts from a much longer report, so follow the link to read it in its entirety.
Highly pathogenic avian influenza A(H5N1) virus infection in farmed minks, Spain, October 2022
Montserrat Agüero1,* , Isabella Monne2,* , Azucena Sánchez1 , Bianca Zecchin2 , Alice Fusaro2 , María José Ruano1 , Manuel del Valle Arrojo3 , Ricardo Fernández-Antonio4 , Antonio Manuel Souto5 , Pedro Tordable5 , Julio Cañás5 , Francesco Bonfante2 , Edoardo Giussani2 , Calogero Terregino2 , Jesús Javier Orejas6
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.
Outbreak description and sampling
On the first week of October, an acute increase in the mortality rate (0.77% vs an expected range of 0.2–0.3%) was identified at an American mink (Neovison vison) farm in the municipality of Carral, in the province A Coruña, Galicia, Spain.
Therefore, on 4 October 2022, the farm clinical veterinarian collected oropharyngeal swabs from two affected animals. The samples, analysed at the Central Veterinary Laboratory (LCV) of Algete (Ministry of Agriculture, Fisheries and Food (MAPA)), tested negative by real-time reverse transcription (RT)-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) , and positive by real-time RT-PCR for HPAI A(H5N1) virus [2,3]. Post-mortem examination revealed haemorrhagic pneumonia or red hepatisation of the lungs as the most notable lesions.
Four of the nine H5N1 virus-positive oropharyngeal swabs collected on 18 October were submitted to the European Reference laboratory (EURL) for avian influenza (AI) in Italy (Istituto Zooprofilattico Sperimentale delle Venezie) for genetic characterisation. Whole genome sequences were generated (GISAID accession numbers: EPI2220590–EPI2220621) and phylogenetically analysed. The analysis of the haemagglutinin (HA) gene segment showed that the HPAI H5N1 viruses from the minks belong to clade 18.104.22.168b (Figure 1). Clustering of the four characterised viral genomes from minks indicates that they are highly related (similarity ranging from 99.8% to 100%) and belong to the A/gull/France/22P015977/2022-like genotype  (Figure 2).
Public health measures
Culling activities started soon after the official order by animal health services on 18 October 2022. Animals were culled in batches of 150–200 animals. By 17 November 2022, all minks at the infected premises were culled and all the carcasses, fomites and waste were destroyed.
The mink farm had a staff of 12 workers, 11 of whom had been in contact with the animals and were also involved in the culling activities. On 13 and 14 October, nasopharyngeal swabs were taken from the 11 asymptomatic workers and all tested negative for avian influenza virus (AIV). A semi-quarantine regimen, intended to avoid any contact with other people, was employed to the exposed workers for 10 days from their last contact with the animals or the farm. In addition, the workers and their cohabitants were instructed to immediately inform public health authorities in case of influenza-like illness, such as runny/stuffy nose, fever, sore throat, cough, muscle or body aches, headaches, in order to initiate testing and follow-up. On 2 November 2022, one of the workers had a runny nose. Real-time RT-PCR against AIV was performed on a nasopharyngeal sample, yielding negative results. Antiviral post-exposure prophylaxis was not prescribed, as more than 48 h had already passed since the potential HPAI H5N1 virus exposure.
We present, to the best of our knowledge, the first report of clade 22.214.171.124b 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 . However, the viruses detected at the mink farm are distinguished from all the clade 126.96.36.199b 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.  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 , 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 [10-14]. In light of this and considering the ongoing HPAI H5N1 panzootic, our findings further highlight the importance of preventing mink infection with such viruses.