H5N1 Hybrid Viruses Bearing 2009/H1N1 Virus Genes Transmit in Guinea Pigs by Respiratory Droplet

In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway rece...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-06, Vol.340 (6139), p.1459-1463
Main Authors: Zhang, Ying, Zhang, Qianyi, Kong, Huihui, Jiang, Yongping, Gao, Yuwei, Deng, Guohua, Shi, Jianzhong, Tian, Guobin, Liu, Liling, Liu, Jinxiong, Guan, Yuntao, Bu, Zhigao, Chen, Hualan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Avian flu
Brain - virology
Cell Line
Data transmission
Disease transmission
Epidemics
Ferrets
Genes
Genes, Viral
Guinea Pigs
H5N1 subtype influenza A virus
Hemagglutinin Glycoproteins, Influenza Virus - chemistry
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Humans
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - pathogenicity
Influenza A Virus, H5N1 Subtype - genetics
Influenza A Virus, H5N1 Subtype - pathogenicity
Influenza virus
Influenza, Human - transmission
Influenza, Human - virology
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Mutation
Neurons
Orthomyxoviridae
Orthomyxoviridae Infections - transmission
Orthomyxoviridae Infections - virology
Reassortant Viruses - genetics
Reassortant Viruses - pathogenicity
Receptors, Cell Surface - metabolism
Receptors, Virus - metabolism
Respiratory diseases
Respiratory System - virology
Reverse Genetics
Ribonucleoproteins - metabolism
Transmission efficiency
Viral Proteins - genetics
Viral Proteins - metabolism
Virulence
Virus Replication
Viruses
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Items that cite this one
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Summary:In the past, avian influenza viruses have crossed species barriers to trigger human pandemics by reassorting with mammal-infective viruses in intermediate livestock hosts. H5N1 viruses are able to infect pigs, and some of them have affinity for the mammalian type α-2,6-linked sialic acid airway receptor. Using reverse genetics, we systematically created 127 reassortant viruses between a duck isolate of H5N1, specifically retaining its hemagglutinin (HA) gene throughout, and a highly transmissible, human-infective H1N1 virus. We tested the virulence of the reassortants in mice as a correlate for virulence in humans and tested transmissibility in guinea pigs, which have both avian and mammalian types of airway receptor. Transmission studies snowed that the H1N1 virus genes encoding acidic polymerase and nonstructural protein made the H5N1 virus transmissible by respiratory droplet between guinea pigs without killing them. Further experiments implicated other H1N1 genes in the enhancement of mammal-to-mammal transmission, including those that encode nucleoprotein, neuraminidase, and matrix, as well as mutations in H5 HA that improve affinity for humanlike airway receptors. Hence, avian H5N1 subtype viruses do have the potential to acquire mammalian transmissibility by reassortment in current agricultural scenarios.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1229455