#18,468
While the media often talks about avian flu - and even HPAI H5N1 - as if it were a single entity, since it emerged in Southeastern China nearly 30 years ago the A/Goose/Guangdong/1/1996 (gs/GD) lineage of HPAI H5Nx has evolved into 10 clades (0-9), dozens of subclades, numerous subtypes, and hundreds of genotypes.As a segmented virus with 8 largely interchangeable parts, the flu virus is like a viral LEGO (TM) set which allows for the creation of a vast number of unique variants. Each of these reassortments is designated by its genotype (e.g. B3.13, D1.1, A2, etc.).During that time we've seen major shifts in dominant subtypes (H5N1 → H5N8 → H5N6 → H5N1), and while clade 2.3.4.4b is dominant globally, other clades (2.3.2.1a in India and 2.3.2.1c in Cambodia) continue to circulate and spill over into humans.
The emergence of new clades, subtypes, or genotypes is sometimes associated with abrupt changes to the behavior (transmissibility, pathogenicity, host range, etc.) of the H5 virus. Sometimes we get lucky, and it attenuates the virus's threat. Sometimes it enhances it.
Two (of many) examples include:
- The 2005 emergence of a new clade 2.2 at Qinghai Lake in Tibet is credited with sparking the initial westward surge of H5N1 from Southeast Asia into Europe and the Middle East.
- Eleven years later, Europe saw its first major avian epizootic, which was caused by a newly reassorted H5N8 virus - first detected around the Ubsu-Nur Lake in Russia - and later carried to Europe by migratory birds.
Over the years most of these viral combinations have fallen by the wayside, unable to thrive or compete against better adapted strains. But each has provided the virus a stepping stone to evolve into the highly diversified, and often chaotic, array of HPAI viruses circulating today.
- B3.13 aka the `bovine' strain affecting dairy cattle in at least 17 states and mildly infecting dozens of humans
- D1.1 a wild bird/poultry strain which has spilled over into > a dozen people in Washington State, severely infected a teenager in British Columbia, and produced a fatal infection in Louisiana.
- D1.2 a wild bird/poultry strain which recently detected in poultry and 2 pigs in Oregon
- D1.3 a recently detected wild bird/poultry strain which has been infection poultry and at least 1 human
All of which brings us to a research report, published yesterday in the EID Journal, that describes a recent reassortment event that is believed to have occurred in the summer of 2023 somewhere near the Baltic Sea.
Within a year this H5N1 clade 2.3.4.4b reassortant, EA-2023-DG virus had spread widely across Northern and Western Europe, affecting at least 11 countries, and causing outbreaks both in wild and domesticated birds, and was detected in at least one mammal (fox).
In these affected countries it became the second most commonly reported genotype (after EA-2021-AB).
Of particular concern, experimental infection of dairy cows in Europe with a local H5N1 strain (see Germany: FLI Statement On Experimental Infection Of Dairy Cows With European H5N1 Virus) used this emerging genotype, and found it replicated efficiently in bovine mammary tissue and could produce adaptive mutations (PB2 E627K) during replication.
While none of this means that EA-2023-DG will be the next `big' thing for H5Nx, it serves to remind us how volatile HPAI H5 viruses are, and how quickly new threats can emerge.
Right now the EA-2023-DG genotype - along with scores of others carried by migratory birds - are headed north to high latitude roosting areas, where they will have ample opportunities to mix and match viral strains.
What we see return with next fall's migration is anyone's guess (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1).
I've only posted some excerpts, so follow the link to read the full report.
ResearchSteven Van Borm, Ann Kathrin Ahrens, Claudia Bachofen, Ashley C. Banyard, Cathrine Arnason Bøe, François-Xavier Briand, Zuzana Dirbakova, Marc Engelsma, Alice Fusaro, Evelien Germeraad, Britt Gjerset, Béatrice Grasland, Frank Harders, Pierre Hostyn, Ari Kauppinen, Bénédicte Lambrecht, Benjamin C. Mollett, Isabella Monne, Alexander Nagy, Anne Pohlmann, Daniel Polzer, Scott M. Reid, Sandra Revilla-Fernandez, Mieke Steensels, Michaela Stätter, Edyta Swieton, Niina Tammiranta, Michele Wyler, Bianca Zecchin, Siamak Zohari, and Simon DellicourAbstractIn Europe, highly pthogenic avian influenza (HPAI) virus circulates in avian wildlife, undergoing frequent reassortment, sporadic introductions in domestic birds, and spillover to mammals. An H5N1 clade 2.3.4.4b reassortant, EA-2023-DG, affecting wild and domestic birds was detected in western Europe in November 2023. Six of its RNA segments came from the EA-2021-AB genotype, but the polymerase basic 2 and polymerase acidic segments originated from low pathogenicity avian influenza viruses.Discrete phylogeographic analyses of concatenated genomes and single polymerase basic 2 and polymerase acidic segments suggested reassortment in summer 2023 near the southwestern Baltic Sea. Subsequent continuous phylogeographic analysis of all concatenated EA-2023-DG genomes highlighted circulation in northwestern Europe until June 2024 and long-distance dispersal toward France, Norway, England, Slovakia, Switzerland, and Austria. Those results illustrate the value of phylodynamic approaches to investigate emergence of novel avian influenza virus variants, trace their subsequent dispersal history, and provide vital clues for informing outbreak prevention and intervention policies.
Discussion
The ongoing panzootic caused predominantly by clade 2.3.4.4b HPAIVs is notorious for its diversifying evolution, including frequent reassortment events that result in an ever-changing range of circulating genotypes (2,6). Reassortment events represent crucial shifts in virus evolution that can affect host range, pathogenicity, and other epidemiologically relevant aspects of the virus phenotype; thus, understanding the dynamics behind the emergence and spread of such novel reassortants is critical. Combining complete avian influenza genomes and exact spatial and temporal sampling data enables detailed reconstruction of virus dispersal during an outbreak (31) and identification of reassortment events (2).
In this study, we analyzed all available full-genome sequences of novel reassortant HPAIV H5N1 genotype EA-2023-DG, which emerged in 2023 in western Europe (10), to reconstruct its genesis and dispersal dynamics. We traced its origin to the southwestern Baltic Sea area in the spring and summer of 2023.
More precisely, most of the genome (i.e., PB1, HA, NP, NA, MP, and NS segments) originated from the dominant EA-2021-AB genotype, and the most recent common ancestor of those EA-2023-DG genomic segments likely emerged in or close to Sweden during summer 2023. As for the PA and PB2 segments, we inferred their origin in Germany, meaning that they could have originated from low pathogenicity avian influenza viruses circulating in Germany during winter and spring 2023, as suggested by others merely on the basis of sequence similarity (10). Overall, our results point toward a local reassortment event that occurred in the southwestern Baltic Sea area, which is in line with the first occurrence of the genotype in southern Finland.
(SNIP)
During its period of circulation, EA-2023-DG became the second most frequent (54 cases) genotype in the countries it affected, but EA-2021-AB remained the dominant genotype with 84 reported cases. Other prevalent genotypes were EA-2023-DB (32 cases), EA-2024-DI (26 cases), EA-2022-BB (16 cases), EA-2021-I (14 cases), and EA-2023-DA (13 cases) (33,34). Ten additional genotypes circulated at lower frequency (<10 cases), reflecting the known diversification potential of H5N1 clade 2.3.4.4b viruses (2).
In vivo experiments following up on the emergence of HPAIV H5N1 in cattle in the United States (35), and its subsequent spillover to other mammals, including cats (35) and exposed humans (36), used an EA-2023-DG genotype virus as a model of contemporary circulating viruses in Europe.
Those studies indicated that these viruses efficiently replicate in bovine mammary tissue and can produce adaptive mutations (PB2 E627K) during replication (37). Those findings underscore the value of phenotypic characterization of currently circulating H5Nx clade 2.3.4.4b viruses, including the newly emerged EA-2023-DG genotype, because the zoonotic potential of the viruses can evolve, driven and shaped by epidemiologic events that could increase the likelihood of spillover to mammals and subsequent adaptation. In response to HPAIV reassortment promiscuity resulting in fast evolution and diversification (2,6), efficient livestock and wildlife surveillance programs including a viral genomic characterization are essential.(Continue . . . . )
In conclusion, although gaps in surveillance data will always exist, we demonstrated that viral genomic data collected from surveillance programs combined with precise spatial and temporal metadata can enable a comprehensive investigation of the genesis of novel AIV reassortants and of their spread dynamics. In addition to viral genetic characterization, such as adaptive mutations and genotyping, these parameters provide vital clues for informing outbreak prevention and intervention policies.
