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Literature detail

The T160A hemagglutinin substitution affects not only receptor binding property but also transmissibility of H5N1 clade 2.3.4 avian influenza virus in guinea pigs.

Min Gu1,2 Qunhui Li1 Ruyi Gao1 Dongchang He1 Yunpeng Xu1 Haixu Xu1 Lijun Xu1,3 Xiaoquan Wang1,2 Jiao Hu1,2 Xiaowen Liu1,2 Shunlin Hu1,2 Daxin Peng1,2,4 Xinan Jiao1,2,4 Xiufan Liu5,6,7
Affiliations 7 institutions
  1. College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China.
  2. Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, 225009, China.
  3. Yangzhou Entry-Exit Inspection and Quarantine Bureau, Yangzhou, Jiangsu, 225009, China.
  4. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, Jiangsu, 225009, China.
  5. College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China. [email protected].
  6. Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu, 225009, China. [email protected].
  7. Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses, Yangzhou, Jiangsu, 225009, China. [email protected].
PMID 28166830 2017 Vet Res eng epublish
PubMed DOI Browse context

Article

Publication summary

We generated and characterized site-directed HA mutants on the genetic backbone of H5N1 clade 2.3.4 virus preferentially binding to α-2,3 receptors in order to identify the key determinants in hemagglutinin rendering the dual affinity to both α-2,3 (avian-type) and α-2,6 (human-type) linked sialic acid receptors of the current clade 2.3.4.4 H5NX subtype avian influenza reassortants. The results show that the T160A substitution resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs, which could be considered as an important molecular marker for assessing pandemic potential of H5 subtype avian influenza isolates.

Amino Acid Substitution Animals Female Guinea Pigs Hemagglutinin Glycoproteins, Influenza Virus Influenza A Virus, H5N1 Subtype Orthomyxoviridae Infections Receptors, Virus Virus Replication

Structured evidence records

Evidence records

4 total
Receptor Usage 2 records
Receptor Usage Extraction confidence 0.95
Key finding

The T160A substitution in H5N1 clade 2.3.4 hemagglutinin increased binding to human-type (α-2,6-linked) sialic acid receptors.

Virus
IAV H5N1
Location
Not specified
Supporting text

The T160A substitution resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs.

Receptors
α-2,6 (human-type) linked sialic acid receptor
Receptor Usage Extraction confidence 0.95
Key finding

H5N1 clade 2.3.4 avian influenza virus hemagglutinin naturally binds α-2,3 (avian-type) sialic acid receptors and can acquire affinity to α-2,6 (human-type) receptors.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

We generated and characterized site-directed HA mutants on the genetic backbone of H5N1 clade 2.3.4 virus preferentially binding to α-2,3 receptors in order to identify the key determinants in hemagglutinin rendering the dual affinity to both α-2,3 (avian-type) and α-2,6 (human-type) linked sialic acid receptors.

Receptors
α-2,3 (avian-type) linked sialic acid receptor
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 0.90
Key finding

The T160A HA substitution in H5N1 clade 2.3.4 virus increased binding to human-type receptors and allowed transmissibility in guinea pigs, demonstrating altered host range.

Virus
IAV H5N1
Location
Not specified
Supporting text

The results show that the T160A substitution resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs.

Method
experimental infection; transmission assay
Experimental system
in vivo animal experiment
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

T160A in the hemagglutinin of H5N1 clade 2.3.4 avian influenza virus increases human-type receptor binding and transmissibility in guinea pigs.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

The T160A substitution resulted in the loss of a glycosylation site at 158N and led not only to enhanced binding specificity for human-type receptors but also transmissibility among guinea pigs.

Genes or proteins
hemagglutinin
Receptors
human-type receptor; sialic acid receptor
Mutations
T160A
Mechanism types
receptor_binding; transmission_fitness; glycosylation_loss