#18,511
A little over a year ago, in Emerg. Microb & Inf.: Emergence of Novel Reassortant H3N3 Avian Influenza viruses, China 2023, we looked at a study which described a new reassortant H3N3 virus in Chinese poultry which included an HA gene from H3N8, an NA gene from H10N3, and internal genes from H9N2 (all zoonotic subtypes).
Despite this impressive pedigree, this reassortant H3N3 virus was not pathogenic in mice, bound preferentially to avian receptor cells, and lacked a number of key mammalian adaptations.
That said, over the past few years we've seen a noticeable uptick in new H3 reassortments emerging out of China (see EID Journal: Evolution of Avian Influenza Virus (H3) with Spillover into Humans, China).
Since all of the known human pandemics (going back 130 years) have sprung from H1, H2, or H3 influenza viruses, we can't afford to ignore new H1, H2, or H3 viruses when they emerge around the world.
Today we've a new report on this H3N3 virus which paints a more complete picture of the virus, finding that it (and other novel H3 reassortants) are spreading in Chinese poultry, and that it carries mutations that may ` . . . increase viral resistance, virulence, and transmission in mammalian hosts.'
While this virus may not be ready for prime time, the rapid evolution of H3 viruses in China is worthy of our attention. Due to its length, I've only posted some excerpts.
Follow the link to read the report in its entirety.
Evidence of an emerging triple-reassortant H3N3 avian influenza virus in China
BMC Genomics volume 25, Article number: 1249 (2024)
Abstract
The H3 subtype of avian influenza virus (AIV) stands out as one of the most prevalent subtypes, posing a significant threat to public health. In this study, a novel triple-reassortant H3N3 AIV designated A/chicken/China/16/2023 (H3N3), was isolated from a sick chicken in northern China.
The complete genome of the isolate was determined using next-generation sequencing, and the AIV-like particles were confirmed via transmission electron microscopy. Subsequent phylogenetic analyses revealed that HA and NA genes of the H3N3 isolate clustered within the Eurasian lineage of AIVs, exhibiting the closest genetic relationship with other H3N3 AIVs identified in China during 2023.
Interestingly, the HA and NA genes of the novel H3N3 isolate were originated from H3N8 and H10N3 AIVs, respectively, and the six internal genes originated from prevalent H9N2 AIVs. These findings indicated the novel H3N3 isolate possesses a complex genetic constellation, likely arising from multiple reassortment events involving H3N8, H9N2, and H10N3 subtype influenza viruses.
Additionally, the presence of Q226 and T228 in the HA protein suggests the H3N3 virus preferentially binds to α-2,3-linked sialic acid receptors. The HA cleavage site motif (PEKQTR/GIF) and the absence of E627K and D701N mutations in PB2 protein classify the virus as a characteristic low pathogenicity AIV.
However, several mutations in internal genes raise concerns about potential increases in viral resistance, virulence, and transmission in mammalian hosts. Overall, this study provides valuable insights into the molecular and genetic characterization of the emerging triple-reassortant H3N3 AIVs, and continued surveillance of domestic poultry is essential for monitoring the H3N3 subtype evolution and potential spread.
(SNIP)
Discussion
In this study, the whole genome sequence of the novel H3N3 isolate was determined by utilizing next-generation sequencing, and the genome was annotated based on the sequence characterization of the reported AIV isolates. The results showed that the genome structure of the novel H3N3 isolate is closely similar to other known AIVs in the GenBank and GISAID EpiFlu™ databases [73].
However, the novel H3N3 strain exhibited a distinct genomic composition compared to other H3 subtype AIVs, displaying high similarity to H3N8, H9N2, and H10N3 influenza viruses (Table 2). These findings classify the H3N3 isolate as a novel triple-reassortant AIV. Meanwhile, phylogenetic analysis revealed that all segments within the novel H3N3 virus genome were clustered in the Eurasian lineage of AIVs. The HA protein, crucial for viral entry into host cells and inducing the production of neutralizing antibodies production [76], exhibited a PEKQTR/GIF cleavage site characteristic of LPAIVs. Additionally, the presence of Q226 and T228 amino acids at the receptor-binding site suggested a preference for avian-like (α-2,3-linked sialic acid) receptors (Table 3) [76,77,78].
However, the results of both nucleotide sequence homology and evolutionary analyses based on the HA gene indicate that this newly H3N3 strain is closely genetically related to a human-derived H3N8 influenza virus (A/China/ZMD-22–2/2022(H3N8)), which was isolated in April 2022 from a four-year-old boy in China experiencing recurrent fever and severe pneumonia [27]. Further studies showed that this human-derived H3N8 influenza virus was likely generated by reassortment of the H3N2, H3N8 and H9N2 AIVs [7, 17]. The PB2 gene is known to significantly influence influenza virus pathogenicity, with the E627K mutation in the PB2 protein associated with zoonotic potential [47]. Previous studies have speculated that it is likely that H3N8 AIVs gained the ability to spill over to humans by recombining with H9N2 viruses with the amino acid mutation at position 627 (E627K) in the PB2 fragment [22, 27]. Notably, the absence of the E627K mutation in the PB2 protein of the novel H3N3 strain suggests a reduced risk to public health (Table 4).
(SNIP)
Considering these reports of novel H3N3 AIVs and the latest information on H3N3 strains in the NCBI and GISAID databases, it suggests that the novel H3N3 AIVs generated by reassortment of H3N8, H9N2, and H10N3 influenza viruses have already appeared in various regions of China, and have a tendency to become more prevalent.
(SNIP)
Conclusions
This paper presents a comprehensive genomic analysis of a newly dectected triple-reassortant H3N3 AIV strain, designated A/chicken/China/16/2023 (H3N3), isolated from a chicken in China during 2023. Comparative genomic studies and phylogenetic analysis revealed that this novel H3N3 virus originated from a triple reassortment event involving H3N8, H9N2, and H10N3 influenza viruses.
Notably, several mutations in the internal genes of the novel H3N3 isolate raise concerns about potential increases in viral resistance, virulence, and transmission in mammalian hosts. This study expands our understanding of triple-reassortant H3N3 AIVs, and underscores the critical need for continued surveillance of these emerging viruses in domestic poultry.
