Rapid adaptation of avian H7N9 virus in pigs.

Lili Xu1 Linlin Bao1 Wei Deng1 Hua Zhu1 Fengdi Li1 Ting Chen1 Qi Lv1 Jing Yuan1 Yanfeng Xu1 Yanhong Li1 Yanfeng Yao1 Songzhi Gu1 Pin Yu1 Honglin Chen2 Chuan Qin3
Affiliations 3 institutions
  1. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Pan Jia Yuan Nan Li No. 5, Chao Yang District, Beijing, China.
  2. State Key Laboratory for Emerging Infectious Diseases, Department of Microbiology and the Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong SAR, China.
  3. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Pan Jia Yuan Nan Li No. 5, Chao Yang District, Beijing, China. Electronic address: [email protected].

Abstract

How the H7N9 avian influenza virus gained the distinct ability to infect humans is unclear. Pigs are an important host in influenza virus ecology because they are susceptible to infection with both avian and human influenza viruses and are often involved in interspecies transmission. Here, we passaged one avian isolate and one human isolate in pigs to examine the mammalian host adaptation of the H7N9 virus. The avian virus replicated to a high titer after one passage, whereas the human isolate replicated poorly after three passages in pig lungs. Sequence analysis found nine substitutions in the HA, NA, M and NS segments of the avian isolate, which enhanced the binding affinity for human-type receptors. These results indicate that avian H7N9 influenza viruses can be easily adapted to pigs and that pigs may act as an important intermediate host for the reassortment and transmission of such novel viruses.

Supporting text Virus Host Location
Adaptation 13 H7N9 influenza virus 4 Mutation 222 Pig 10 Receptor binding 30 Adaptation, Physiological 33 Animals 1948 Birds 212 Humans 1440 Influenza A Virus, H7N9 Subtype 87 Influenza in Birds 341 Influenza, Human 286 Orthomyxoviridae Infections 228 Sus scrofa 30 Swine 258 Swine Diseases 153

Evidence records

4 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE1684
Key finding

Pigs may act as an intermediate host facilitating reassortment and transmission of avian H7N9 influenza viruses.

Virus
Host
Location
Not specified
Supporting text

These results indicate that avian H7N9 influenza viruses can be easily adapted to pigs and that pigs may act as an important intermediate host for the reassortment and transmission of such novel viruses.

Method
serial passage in pigs | sequence analysis of viral segments
Sample type
pig lungs
Experimental Infection
2 records · 1 evidence types
Evidence type
2 records
OVE1681
Key finding

An avian H7N9 influenza virus isolate replicated efficiently in pigs during experimental passage, indicating susceptibility of pigs to the avian strain.

Virus
Host
Location
Not specified
Supporting text

Here, we passaged one avian isolate and one human isolate in pigs to examine the mammalian host adaptation of the H7N9 virus. The avian virus replicated to a high titer after one passage in pig lungs.

Method
experimental infection | viral replication assay | serial passage
Sample type
pig lungs
Experimental system
animal challenge model (experimental passage in pigs)
OVE1682
Key finding

A human H7N9 influenza virus isolate replicated poorly in pigs after serial passage, showing limited susceptibility of pigs to the human strain.

Virus
Host
Location
Not specified
Supporting text

The avian virus replicated to a high titer after one passage, whereas the human isolate replicated poorly after three passages in pig lungs.

Method
experimental infection | viral replication assay | serial passage
Sample type
pig lungs
Experimental system
animal challenge model (experimental passage in pigs)
Functional Mechanism
1 records · 1 evidence types
Evidence type
1 records
OVE1683
Key finding

Nine amino acid substitutions in the HA, NA, M, and NS segments of an avian H7N9 influenza virus enhanced binding to human-type receptors after passage in pigs.

Virus
Host
Not specified
Location
Not specified
Supporting text

Sequence analysis found nine substitutions in the HA, NA, M and NS segments of the avian isolate, which enhanced the binding affinity for human-type receptors.

Genes or proteins
HA | NA | M | NS
Receptors
human-type receptors
Mutations
nine amino acid substitutions
Mechanism types
receptor binding | host-range expansion