#18,589
The superpower of influenza A viruses is their ability for different subtypes to co-infect a host, swap genetic material, and generate a new `hybrid' virus; a reassortant. This reassortment can generate new genotypes, or - if the HA and NA are involved - a new subtype.
Reassortment - or Antigenic`Shift' - can produce abrupt changes in the behavior of the generated hybrid. Most are evolutionary failures, unable to compete with its parental strains. But every once in awhile, a new, `improved', virus emerge.
As any virologist will tell you; `Shift Happens'.
Reassortment is the process that enabled an avian H5N1 virus (B3.13) to infect cattle, and has recently produced a more virulent D1.1 genotype, which is spreading rapidly across the nation. It produced a new H5N9 subtype in California poultry, and it could potentially lead to a hybrid of seasonal and avian flu sometime in the future (see Preprint: Intelligent Prediction & Biological Validation of the High Reassortment Potential of Avian H5N1 and Human H3N2 Influenza Viruses).
Today we have a report, published this week in Emerging Microbes & Infections, of the discovery of an HPAI H5N2 clade 2.3.4.4b virus in Egypt, one that came about through the merger of the H5N1 virus and the ubiquitous, and highly mutable, LPAI H9N2 virus.
We've often discussed the role that H9N2 has played in the creation of some of the most dangerous HPAI viruses, including H5N1, H5N6, H10N3, and H7N9 (see Transboundary & Emerging Dis.: The H5N6 Virus Containing Internal Genes From H9N2 Exhibits Enhanced Pathogenicity and Transmissibility).
First the link and some excerpts from the study, after which I'll return with a postscript.While much as been made over the fact that humans may have some limited cross-immunity to the N1 component of H5N1, a new subtype - sporting an N2 or an N9 surface gene - might prove far more problematic.
Rabeh El-Shesheny,Mokhtar Gomaa,Mohamed El Sayes,Mina Nabil Kamel,Ahmed El Taweel,Omnia Kutkat, show all
Article: 2455601 | Accepted author version posted online: 27 Jan 2025
Cite this article https://doi.org/10.1080/22221751.2025.2455601
Abstract
Reassortant highly pathogenic avian influenza A(H5N2) clade 2.3.4.4.b viruses were detected from ducks and environmental samples in Egypt, June 2024. Genomic and phylogenetic analyses revealed a novel genotype produced by reassortment of an A(H5N1) clade 2.3.3.4b virus with an A(H9N2) G1-like virus. Monitoring the spread of this virus is important.
Egypt has experienced repeated outbreaks of highly pathogenic avian influenza (HPAI) viruses of the H5 goose/Guangdong lineage since 2006, causing devastating losses to the poultry industry and directly affecting food security. During the past and current decades, several clades of HPAI viruses were detected. Most recently, clade 2.3.4.4b A(H5N1) was introduced into Egypt during the winter of 2021 and replaced the previous HPAI A(H5N8) clade 2.3.4.4b strains [1]. Phylogenetic analyses showed that these viruses retained genomic characteristics similar to Eurasian strains, suggesting continuous evolution and adaptation of the virus in the region. These introductions have resulted in serious economic repercussions on the poultry sector in this country. Furthermore, a total of 359 confirmed cases of human infection with HPAI (H5N1) were reported from Egypt to the World Health Organization (WHO).
In addition to the HPAI (H5Nx) viruses, low pathogenic avian influenza (LPAI) H9N2 subtype is widely circulating in poultry in Egypt since the beginning of 2010 [2,3]. The co-circulation of both subtypes, A(H5N1) and A(H9N2) viruses, was observed in our active surveillance [4]. Furthermore, we detected H5N1/H9N2 co-infection in the same domestic poultry host [4]. Two studies reported natural reassortment events in Egypt between H5N1 and H9N2 viruses [5,6]. Furthermore, four cases of human infection with H9N2 AIV were reported in Egypt in 2014-2015 [7].
These co-circulation and co-infection events provide appropriate conditions for the emergence of novel reassortant viruses with unknown biological characteristics and zoonotic potential. Here, we characterized the complete genome of five HPAI (H5N2) novel virus strains from Egypt and report the identification and characterization of a novel natural reassortant HPAI (H5N1) virus that obtained the NA and NS genes from an H9N2 virus.
The Study
Through active surveillance of influenza viruses in poultry and wild birds in Egypt, we detected five HPAI A(H5N2) viruses from live bird markets (LBMs) in June 2024.
Three viruses, A/MuscovyDuck/Egypt/BA21820OP/2024(H5N2), A/MuscovyDuck/Egypt/BA21821C/2024(H5N2), and A/MuscovyDuck/Egypt/BA21822OP/2024(H5N2) originated from duck swabs, while two viruses, A/environment/Egypt/BA21829W/2024(H5N2) and A/Environment/Egypt/BA21832W /2024(H5N2) were detected from water samples from poultry waterers.(SNIP)
To identify mutations that may be associated with virulence, pathogenicity, and transmission in mammals, we analyzed the amino acid sequences of the novel viruses. The E627 K or D701N substitutions in PB2 that increase virulence in mammals were not detected. However, all five isolates had amino acid substitutions that included L89 V, G309D, T339 K, and I504 V in PB2, known to increase virulence in mice [9], and A515 T in PA, known to increase polymerase activity [10]. All the strains expressed PB1-F2 of 90 amino acids and had an N66S mutation (Table S3). S31N amantadine resistance marker in M2 protein [11] was detected in our strains. Our analyses showed that NS1 protein contains amino acid substitutions P42S and V149A which might increase replication efficiency as well as virulence in mammals (Table S3).
Discussion
H9N2 avian influenza viruses (AIVs) play a critical role in the evolution of influenza viruses as they are donors of genetic material to emerging zoonotic viruses such as H5Nx, H7N9, and H10N8 AIVs. The H5 HPAI of different clades reassorted with N2 genes in various countries but the clade 2.3.4.4c showed the highest number of reassortment events (n = 536 strains) (Table S4). The reassortments of H5Nx clade 2.3.4.4b HPAI and LPAI viruses were reported in various countries. Novel reassortments of clade 2.3.4.4 HPAI and LPAI from North America were responsible for outbreaks in domestic cattle and spillover into poultry as well as mammals [12,13]. In a previous study, the insertion of the N2 gene from an H9N2 virus into an H5 vaccine strain on a PR8 backbone increased its replication as compared to a strain that had the N1 [14]. Hence, those novel viruses have the potential to display biological features that may enhance their virulence, pathogenicity, replication, and transmission in avian and mammalian hosts.
Our study represents the first report of detection and genomic characterization of HPAI H5N2 clade 2.3.4.4b in Egypt. The genomic characteristics of those viruses revealed mutations that could have important implications on animal and human health. Further surveillance and biological studies are urgently required to assess the potential of spread of this virus and evaluate its biological characteristic to investigate its zoonotic potential and understand its associated risks.
Six years ago, in J. Virology: Genetic Compatibility of Reassortants Between Avian H5N1 & H9N2 Influenza Viruses, we looked at the results of an Egyptian lab experiment which found that reassortments between H5N1 and H9N2 could produce multiple viable, and potentially dangerous, progeny.
To evaluate the potential public health risk of reassortants of these viruses, we used reverse genetics to generate the 63 possible reassortants derived from contemporary Egyptian H5N1 and H9N2 viruses, containing the H5N1 surface gene segments and combinations of the H5N1 and H9N2 internal gene segments, and analyzed their genetic compatibility, replication ability, and virulence in mice. Genes in the reassortants showed remarkably high compatibility.
The replication of most reassortants was higher than the parental H5N1 virus in human cells. Six reassortants were thought to emerge in birds under neutral or positive selective pressure, and four of them had higher pathogenicity in vivo than the parental H5N1 and H9N2 viruses.
Our results indicated that H5N1-H9N2 reassortants could be transmitted efficiently to mammals with significant public health risk if they emerge in Egypt, although the viruses might not emerge frequently in birds.Less than a year later, in EID Journal: Novel Reassortant HPAI A(H5N2) Virus in Broiler Chickens, Egypt, we saw a new proof of concept in the field, after an HPAI H5N8 virus reassorted with an LPAI H9N2 virus, and produced a new HPAI H5N2 virus in Egyptian poultry.
While the world seems to be focused on HPAI in North America, this should remind us that H5Nx viruses are occurring all around the globe, and that a new threat could emerge anytime, and from just about anywhere.
Stay tuned.
