Literature detail

A Highly Pathogenic Avian H7N9 Influenza Virus Isolated from A Human Is Lethal in Some Ferrets Infected via Respiratory Droplets.

Masaki Imai¹ Tokiko Watanabe² Maki Kiso² Noriko Nakajima³ Seiya Yamayoshi² Kiyoko Iwatsuki-Horimoto² Masato Hatta⁴ Shinya Yamada² Mutsumi Ito² Yuko Sakai-Tagawa² Masayuki Shirakura⁵ Emi Takashita⁵ Seiichiro Fujisaki⁵ Ryan McBride⁶ Andrew J Thompson⁶ Kenta Takahashi³ Tadashi Maemura² Hiromichi Mitake² Shiho Chiba⁴ Gongxun Zhong⁴ Shufang Fan⁴ Kohei Oishi² Atsuhiro Yasuhara² Kosuke Takada² Tomomi Nakao² Satoshi Fukuyama² Makoto Yamashita² Tiago J S Lopes^7,4 Gabriele Neumann⁴ Takato Odagiri⁵ Shinji Watanabe⁵ Yuelong Shu⁸ James C Paulson⁶ Hideki Hasegawa³ Yoshihiro Kawaoka^7,9,10

Affiliations 10 institutions

Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: [email protected].
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA.
Influenza Virus Research Center, National Institute of Infectious Diseases, Musashimurayama, Tokyo 208-0011, Japan.
Departments of Molecular Medicine & Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan
National Institute for Viral Disease Control and Prevention, China Centers for Disease Control and Prevention, Beijing 102206, China.
Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Sciences, University of Wisconsin-Madison, Madison, WI 53711, USA
Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan. Electronic address: [email protected].

PMID 29056430 2017 Cell Host Microbe eng ppublish

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Article

Publication summary

Low pathogenic H7N9 influenza viruses have recently evolved to become highly pathogenic, raising concerns of a pandemic, particularly if these viruses acquire efficient human-to-human transmissibility. We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation. All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals. Neuraminidase inhibitors showed limited effectiveness against these viruses in vivo, but the viruses were susceptible to a polymerase inhibitor. These results suggest that the highly pathogenic H7N9 virus has pandemic potential and should be closely monitored.

antiviral sensitivity ferrets highly pathogenic avian influenza H7N9 viruses mice nonhuman primates pathogenicity receptor-binding specificity replication capacity transmissibility Animals Antiviral Agents Brain Cell Line Chickens Conjunctiva Disease Models, Animal Enzyme Inhibitors Ferrets

Structured evidence records

Evidence records

7 total

Host Range Experiment 3 records

Host Range Experiment Extraction confidence 0.95

Key finding

Highly pathogenic avian H7N9 influenza virus replicated efficiently in ferrets and was transmissible via respiratory droplets, demonstrating mammalian host susceptibility and transmission potential.

Virus

Host

Location

Supporting text

The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus. All viruses transmitted among ferrets via respiratory droplets.

Method: experimental infection; respiratory droplet transmission assay
Experimental system: in vivo animal experiment

Host Range Experiment Extraction confidence 0.90

Key finding

Highly pathogenic avian H7N9 influenza virus replicated efficiently in mice and was more pathogenic than the low pathogenic strain.

Virus

Host

Location

Supporting text

The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic in mice and ferrets than the low pathogenic H7N9 virus.

Method: experimental infection; replication assay
Experimental system: in vivo animal experiment

Host Range Experiment Extraction confidence 0.85

Key finding

Highly pathogenic avian H7N9 influenza virus replicated efficiently in nonhuman primates, indicating susceptibility of this mammalian host.

Virus

Host

Location

Supporting text

The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates.

Method: experimental infection; replication assay
Experimental system: in vivo animal experiment

Cross Species Transmission 1 records

Cross Species Transmission Extraction confidence 0.90

Key finding

Highly pathogenic avian H7N9 influenza virus transmitted among ferrets via respiratory droplets, indicating animal-to-animal transmission of an avian-origin virus in mammals.

Virus

Host

Location

Supporting text

All viruses transmitted among ferrets via respiratory droplets, and the neuraminidase-sensitive variant killed several of the infected and exposed animals.

Method: experimental infection
Study design: animal experiment
Transmission direction: animal-to-animal

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.75

Key finding

Comparative analysis revealed multiple variants within a highly pathogenic H7N9 influenza isolate, representing neuraminidase inhibitor–sensitive and –resistant subpopulations that have evolved from low pathogenic progenitors.

Virus

Host

Location

Supporting text

Genes or proteins: neuraminidase
Analysis methods: comparative analysis

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.85

Key finding

Highly pathogenic H7N9 influenza virus variants showed molecular adaptation associated with increased replication and pathogenicity in mammalian hosts and the emergence of a neuraminidase inhibitor-resistant subpopulation.

Virus

Host

Location

Supporting text

We compared a low pathogenic H7N9 virus with a highly pathogenic isolate, and two of its variants that represent neuraminidase inhibitor-sensitive and -resistant subpopulations detected within the isolate. The highly pathogenic H7N9 viruses replicated efficiently in mice, ferrets, and/or nonhuman primates, and were more pathogenic than the low pathogenic H7N9 virus, with the exception of the neuraminidase inhibitor-resistant virus, which showed mild-to-moderate attenuation.

Genes or proteins: neuraminidase
Mechanism types: pathogenicity; replication_efficiency; immune_escape

Spillover Event 1 records

Spillover Event Extraction confidence 0.95

Key finding

A highly pathogenic avian H7N9 influenza virus was isolated from a human, demonstrating avian-to-human transmission.

Virus

Host

Location

Supporting text

A highly pathogenic avian H7N9 influenza virus was isolated from a human, indicating direct infection of a human by an avian-origin H7N9 virus.

Method: virus isolation
Study design: laboratory isolation
Transmission direction: animal-to-human

Citation context

References

56 references

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PMID 22440915	Fitness of neuraminidase inhibitor-resistant influenza A viruses	Baranovich	2011
PMID 23842497 In OmniVira	Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.	Belser	2013
PMID 22056389	In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity	Chen	2012
PMID 24162312 In OmniVira	Adaptation of novel H7N9 influenza A virus to human receptors.	Dortmans	2013
PMID 19476650	Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis	Furuse	2009
PMID 23658443	Comparison of the levels of infectious virus in respirable aerosols exhaled by ferrets infected with influenza viruses exhibiting diverse transmissibility phenotypes	Gustin	2013
PMID 11546875	Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses	Hatta	2001
PMID 22723413 In OmniVira	Airborne transmission of influenza A/H5N1 virus between ferrets.	Herfst	2012
PMID 18481363	Simultaneous inference in general parametric models	Hothorn	2008
PMID 22722205 In OmniVira	Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.	Imai	2012
PMID 19672242	In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses	Itoh	2009
PMID 10365160	Exacerbation of influenzavirus pneumonia by intranasal administration of surfactant in a mouse model	Iwasaki	1999
PMID 19493997	Reassortment between avian H5N1 and human H3N2 influenza viruses in ferrets: a public health risk assessment	Jackson	2009
PMID 28580899	Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China	Ke	2017
PMID 24144478	A replication-incompetent influenza virus bearing the HN glycoprotein of human parainfluenza virus as a bivalent vaccine	Kobayashi	2013
PMID 20592108	Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam	Le	2010
PMID 16140781 In OmniVira	Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model.	Li	2005
PMID 16000410	Highly pathogenic H5N1 influenza virus infection in migratory birds	Liu	2005
PMID 16880383 In OmniVira	Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model.	Maines	2006
PMID 12788625	Replication and transmission of influenza viruses in Japanese quail	Makarova	2003
PMID 9499107	Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors	McKimm-Breschkin	1998
PMID 19574348	Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets	Munster	2009
PMID 20519405	Insertion of a multibasic cleavage motif into the hemagglutinin of a low-pathogenic avian influenza H6N1 virus induces a highly pathogenic phenotype	Munster	2010
PMID 24899188	Disease severity is associated with differential gene expression at the early and late phases of infection in nonhuman primates infected with different H5N1 highly pathogenic avian influenza viruses	Muramoto	2014
PMID 25812763	Transmission of influenza A viruses	Neumann	2015
PMID 10430945	Generation of influenza A viruses entirely from cloned cBNAs	Neumann	1999
PMID 23383167	Sample size considerations for one-to-one animal transmission studies of the influenza A viruses	Nishmra	2013
PMID 1660837	Efficient selection for high-expression transfectants with a novel eukaryotic vector	Niwa	1991
PMID 21880840	Replication-incompetent influenza A viruses that stably express a foreign gene	Ozawa	2011
PMID 28017661	Recent H3N2 Viruses Have Evolved Specificity for Extended, Branched Human-type Receptors, Conferring Potential for Increased Avidity	Peng	2017
PMID 26334134	Development of high-yield influenza A virus vaccine viruses	Ping	2015
PMID 23950563 In OmniVira	H7N9 influenza viruses interact preferentially with α2,3-linked sialic acids and bind weakly to α2,6-linked sialic acids.	Ramos	2013
PMID 27558428	Reduction of Neuraminidase Activity Exacerbates Disease in 2009 Pandemic Influenza Virus-Infected Mice	Ranadheera	2016
PMID 23925116 In OmniVira	Limited airborne transmission of H7N9 influenza A virus between ferrets.	Richard	2013
PMID 6868370	Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin	Rogers	1983
PMID 22278228	The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets	Schrauwen	2012
PMID 28250340	Global concern regarding the fifth epidemic of human infection with avian influenza A (H7N9) virus in China	Shen	2017
PMID 24009358 In OmniVira	Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses.	Shi	2013
PMID 25409547	The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication	Song	2014
PMID 18672252 In OmniVira	Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity.	Stevens	2008
PMID 16543414 In OmniVira	Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus.	Stevens	2006
PMID 8230444	Rescue of an influenza A virus wild-type PB2 gene and a mutant derivative bearing a site-specific temperature-sensitive and attenuating mutation	Subbarao	1993
PMID 22205751	The multibasic cleavage site of the hemagglutinin of highly pathogenic A/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals	Suguitan	2012
PMID 28583578	Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013–17: an epidemiological study of laboratory-confirmed case series	Wang	2017
PMID 23842494	Characterization of H7N9 influenza A viruses isolated from humans	Watanabe	2013
PMID 26782141	PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses	Xiao	2016
PMID 23615615 In OmniVira	Receptor binding by a ferret-transmissible H5 avian influenza virus.	Xiong	2013
PMID 23787694 In OmniVira	Receptor binding by an H7N9 influenza virus from humans.	Xiong	2013
PMID 16189083	Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility	Yen	2005
PMID 28390707	Human infections with recently-emerging highly pathogenic H7N9 avian influenza virus in China	Zhang	2017
PMID 23868922	H7N9 influenza viruses are transmissible in ferrets by respiratory droplet	Zhang	2013
PMID 19605485	Single-reaction genomic amplification accelerates sequencing and vaccine production for classical and Swine origin human influenza a viruses	Zhou	2009
PMID 28409054	Sudden increase in human infection with avian influenza A(H7N9) virus in China, September–December 2016	Zhou	2017
PMID 23704376	Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs	Zhu	2013
PMID 26391278	Dual E627K and D701N mutations in the PB2 protein of A(H7N9) influenza virus increased its virulence in mammalian models	Zhu	2015
PMID 28537546 In OmniVira	Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017.	Zhu	2017

Evidence overview

Evidence 7

Types 5

Virus 1

Host 5

Evidence types

Host Range Experiment 3 Cross Species Transmission 1 Genomic Evolution 1 Molecular Adaptation 1 Spillover Event 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Cell host & microbe
Volume / Issue / Pages: 22 / 5 / 615-626.e8
ISSN: 1934-6069
Journal country: United States
DOI: 10.1016/j.chom.2017.09.008