Literature detail

Novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 virus have been detected in poultry and caused multiple human infections in China.

Wenli Gu1 Jianzhong Shi1 Pengfei Cui1 Cheng Yan1 Yaping Zhang1 Congcong Wang1 Yuancheng Zhang1 Xin Xing1 Xianying Zeng1 Liling Liu1 Guobin Tian1 Yasuo Suzuki2 Chengjun Li1,3 Guohua Deng1 Hualan Chen1,3
Affiliations 3 institutions
  1. State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, CAAS, Harbin, People's Republic of China.
  2. Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
  3. Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, People's Republic of China.
PMID 35380505 2022 Emerg Microbes Infect eng ppublish
PubMed DOI Browse context

Article

Publication summary

The globally circulating H5N8 avian influenza viruses bearing the clade 2.3.4.4b hemagglutinin (HA) gene are responsible for the loss of more than 33 million domestic poultry since January 2020. Moreover, the H5N8 viruses have reassorted with other avian influenza viruses and formed H5N1, H5N2, H5N3, H5N4, and H5N5 viruses in Europe, Africa, and North America. In this study, we analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans, and found these viruses formed seven different genotypes by deriving the clade 2.3.4.4b HA gene of H5N8 viruses, the neuraminidase of domestic duck H5N6 viruses, and internal genes of different viruses that previously circulated in domestic ducks and wild birds in China. Two of these genotypes (genotype 3 and genotype 6) have caused human infections in multiple provinces. The H5N6 viruses isolated from poultry have distinct pathotypes in mice; some of them replicate systemically and are highly lethal in mice. Although these viruses exclusively bind to avian-type receptors, it is worrisome that they may obtain key mutations that would increase their affinity for human-type receptors during replication in humans. Our study indicates that the novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 viruses were generated through reassortment in domestic ducks and may have spread across a wide area of China, thereby posing a new challenge to the poultry industry and human health. Our findings emphasize the importance of careful monitoring, evaluation, and control of the H5N6 viruses circulating in nature.

Avian influenza virus clade2.3.4.4b evolution H5N6 pathogenicity receptor-binding properties Influenza A virus Influenza A Virus, H5N1 Subtype Influenza A Virus, H5N2 Subtype Influenza A Virus, H5N8 Subtype Influenza in Birds Poultry Diseases Animals Birds China Ducks Hemagglutinins Humans

Structured evidence records

Evidence records

6 total
2 records
Extraction confidence 0.90
Key finding

Genome-based analysis showed H5N6 viruses from poultry and humans in China are reassortants incorporating the clade 2.3.4.4b HA gene from H5N8 viruses and internal genes from domestic duck and wild bird viruses.

Virus
Host
Location
Not specified
Supporting text

We analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans, and found these viruses formed seven different genotypes by deriving the clade 2.3.4.4b HA gene of H5N8 viruses, the neuraminidase of domestic duck H5N6 viruses, and internal genes of different viruses that previously circulated in domestic ducks and wild birds in China.

Genes or proteins
HA; neuraminidase; internal genes
Analysis methods
genomic analysis; phylogenetic analysis
Extraction confidence 0.90
Key finding

H5N6 viruses isolated from humans in China were genomic reassortants sharing the clade 2.3.4.4b HA gene from H5N8 viruses and internal genes from avian-origin viruses, showing cross-species evolutionary relationships.

Virus
Location
Not specified
Supporting text

We analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans, and found these viruses formed seven different genotypes by deriving the clade 2.3.4.4b HA gene of H5N8 viruses, the neuraminidase of domestic duck H5N6 viruses, and internal genes of different viruses that previously circulated in domestic ducks and wild birds in China.

Genes or proteins
HA; neuraminidase; internal genes
Analysis methods
genomic analysis; phylogenetic analysis
1 records
Extraction confidence 0.85
Key finding

Poultry-origin H5N6 viruses were experimentally shown to replicate systemically and cause high lethality in mice, demonstrating differences in mammalian pathogenicity and exclusive avian-type receptor binding.

Virus
Location
Not specified
Supporting text

The H5N6 viruses isolated from poultry have distinct pathotypes in mice; some of them replicate systemically and are highly lethal in mice. Although these viruses exclusively bind to avian-type receptors, it is worrisome that they may obtain key mutations that would increase their affinity for human-type receptors during replication in humans.

Method
experimental infection; receptor-binding assay
Experimental system
in vivo animal experiment
1 records
Extraction confidence 0.97
Key finding

Novel H5N6 viruses were generated by reassortment involving H5N8 clade 2.3.4.4b HA and other avian influenza genes, and these reassortants infected both poultry and humans in China.

Host
Not specified
Location
Not specified
Supporting text

Our study indicates that the novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 viruses were generated through reassortment in domestic ducks and may have spread across a wide area of China, thereby posing a new challenge to the poultry industry and human health.

Event type
reassortment
Genes or segments
HA
1 records
Extraction confidence 0.98
Key finding

H5N6 avian influenza viruses originating from poultry caused human infections in multiple provinces in China, demonstrating animal-to-human spillover.

Virus
Location
Supporting text

We analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans, and found that two of these genotypes (genotype 3 and genotype 6) have caused human infections in multiple provinces in China.

Method
virus isolation; genetic analysis
Study design
genomic surveillance
Transmission direction
animal-to-human
Geographic raw
China
Country inferred
China
1 records
Extraction confidence 0.90
Key finding

H5N6 avian influenza viruses were isolated from poultry in China, demonstrating active surveillance of circulating viruses among domestic ducks and poultry.

Virus
Host
Location
Supporting text

In this study, we analyzed 15 H5N6 viruses isolated from poultry and seven H5N6 viruses isolated from humans ... Our study indicates that the novel H5N6 reassortants ... may have spread across a wide area of China, thereby posing a new challenge to the poultry industry and human health.

Geographic raw
China
Country inferred
China