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Literature detail

Pathobiological features of a novel, highly pathogenic avian influenza A(H5N8) virus.

Young-Il Kim1 Philippe Noriel Q Pascua1 Hyeok-Il Kwon1 Gyo-Jin Lim1 Eun-Ha Kim1 Sun-Woo Yoon2 Su-Jin Park1 Se Mi Kim1 Eun-Ji Choi1 Young-Jae Si1 Ok-Jun Lee1 Woo-Sub Shim1 Si-Wook Kim1 In-Pil Mo3 Yeonji Bae3 Yong Taik Lim4 Moon Hee Sung5,6 Chul-Joong Kim7 Richard J Webby8 Robert G Webster8 Young Ki Choi1
Affiliations 8 institutions
  1. College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 361-763, Korea.
  2. Viral Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology , Daejeon 305-806, Korea.
  3. College of Veterinary Medicine, Chungbuk National University , Cheongju 361-763, Korea.
  4. SKKU Advanced Institute of Technology and Department of Chemical Engineering, Sungkyunkwan University , Suwon 440-746, Korea.
  5. Department of Advanced Fermentation Fusion Science & Technology, Kookmin University , Seoul 136-702, Korea
  6. BioLeaders Corporation, Yongsandong, Yuseong-gu, Daejeon 305-500, Korea.
  7. College of Veterinary Medicine, Chungnam National University , Daejeon 305-764, Korea.
  8. Department of Infectious Diseases, St. Jude Children's Research Hospital , Memphis, TN 38105-3678, USA.
PMID 26038499 2014 Emerg Microbes Infect eng ppublish
PubMed DOI Browse context

Article

Publication summary

The endemicity of highly pathogenic avian influenza (HPAI) A(H5N1) viruses in Asia has led to the generation of reassortant H5 strains with novel gene constellations. A newly emerged HPAI A(H5N8) virus caused poultry outbreaks in the Republic of Korea in 2014. Because newly emerging high-pathogenicity H5 viruses continue to pose public health risks, it is imperative that their pathobiological properties be examined. Here, we characterized A/mallard duck/Korea/W452/2014 (MDk/W452(H5N8)), a representative virus, and evaluated its pathogenic and pandemic potential in various animal models. We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks. Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues. In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses. It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding. Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection. With their potential to become established in ducks, continued circulation of A(H5N8) viruses could alter the genetic evolution of pre-existing avian poultry strains. Overall, detailed virological investigation remains a necessity given the capacity of H5 viruses to evolve to cause human illness with few changes in the viral genome.

avian influenza virus genetic evolution HPAI A(H5N8) migratory waterfowl reassortment

Structured evidence records

Evidence records

13 total
Host Range Experiment 7 records
Host Range Experiment Extraction confidence 1.00
Key finding

The H5N8 virus was lethal in chickens but showed attenuated pathogenicity while remaining transmissible in ducks.

Virus
IAV H5N8
Location
Not specified
Supporting text

MDk/W452(H5N8) replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Method
experimental infection
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

The H5N8 virus was attenuated in ducks but efficiently transmitted among them.

Virus
IAV H5N8
Location
Not specified
Supporting text

MDk/W452(H5N8) replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Method
experimental infection; transmission assay
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

The H5N8 virus showed detectable human virus-like receptor binding and replication in human respiratory tract tissues.

Virus
IAV H5N8
Location
Not specified
Supporting text

Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues.

Method
replication assay; receptor-binding assay
Sample type
respiratory tract
Experimental system
ex vivo
Host Range Experiment Extraction confidence 1.00
Key finding

The H5N8 virus exhibited moderate pathogenicity and limited tissue tropism in mice compared to H5N1 viruses.

Virus
IAV H5N8
Location
Not specified
Supporting text

In mice, MDk/W452(H5N8) was moderately pathogenic and had limited tissue tropism relative to previous HPAI A(H5N1) viruses.

Method
experimental infection
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

The H5N8 virus caused moderate nasal wash titers in inoculated ferrets and limited seroconversion in direct-contact ferrets.

Virus
IAV H5N8
Location
Not specified
Supporting text

It also induced moderate nasal wash titers in inoculated ferrets; additionally, it was recovered in extrapulmonary tissues and one of three direct-contact ferrets seroconverted without shedding.

Method
experimental infection; contact transmission assay
Sample type
nasal wash; extrapulmonary tissues
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

Domesticated cats were more susceptible than dogs to H5N8 virus infection.

Virus
IAV H5N8
Location
Not specified
Supporting text

Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection.

Method
experimental infection
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 1.00
Key finding

Dogs were less susceptible than cats to H5N8 virus infection.

Virus
IAV H5N8
Location
Not specified
Supporting text

Moreover, domesticated cats appeared to be more susceptible than dogs to virus infection.

Method
experimental infection
Experimental system
in vivo animal experiment
Cross Species Transmission 2 records
Cross Species Transmission Extraction confidence 0.80
Key finding

Highly pathogenic avian influenza A(H5N8) virus transmitted from wild migratory waterfowl to domestic poultry, being lethal in chickens and transmissible among ducks.

Virus
IAV H5N8
Location
China Eastern China, China
Supporting text

MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Method
pathogenicity testing; virus isolation; reassortment analysis
Study design
animal experiment
Transmission direction
animal-to-animal
Geographic raw
eastern China
Country inferred
China
Cross Species Transmission Extraction confidence 0.80
Key finding

The HPAI A(H5N8) virus transmitted among ducks with reduced pathogenicity compared to chickens.

Virus
IAV H5N8
Host
Anas Anas
Location
South Korea South Korea
Supporting text

MDk/W452(H5N8) was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Method
experimental infection; pathogenicity testing
Study design
animal experiment
Transmission direction
animal-to-animal
Geographic raw
Republic of Korea
Country inferred
South Korea
Receptor Usage 2 records
Receptor Usage Extraction confidence 1.00
Key finding

The H5N8 virus primarily binds avian-like receptors but also demonstrates detectable binding to human-like receptors, supporting partial human receptor compatibility.

Virus
IAV H5N8
Location
Not specified
Supporting text

Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues.

Receptors
avian-like virus receptors
Receptor Usage Extraction confidence 1.00
Key finding

The H5N8 virus exhibited detectable binding to human-like receptors, indicating potential human receptor compatibility.

Virus
IAV H5N8
Location
Not specified
Supporting text

Despite predominant attachment to avian-like virus receptors, MDk/W452(H5N8) also exhibited detectable human virus-like receptor binding and replicated in human respiratory tract tissues.

Receptors
human virus-like receptor
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.80
Key finding

The avian influenza A(H5N8) virus A/mallard duck/Korea/W452/2014 emerged through reassortment of wild bird viruses carried by migratory waterfowl in eastern China, reflecting genomic evolution underlying its appearance.

Virus
IAV H5N8
Host
Anatidae
Location
Not specified
Supporting text

We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Analysis methods
reassortment analysis
Recombination Or Reassortment 1 records
Recombination Or Reassortment Extraction confidence 1.00
Key finding

A/mallard duck/Korea/W452/2014 (H5N8) originated from reassortment of wild bird influenza viruses in eastern China and shows systemic replication and lethality in chickens while being attenuated in ducks.

Virus
IAV H5N8
Host
Not specified
Location
Not specified
Supporting text

We found that MDk/W452(H5N8), which originated from the reassortment of wild bird viruses harbored by migratory waterfowl in eastern China, replicated systemically and was lethal in chickens, but appeared to be attenuated, albeit efficiently transmitted, in ducks.

Event type
reassortment