Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.

Jessica A Belser1 Kortney M Gustin Melissa B Pearce Taronna R Maines Hui Zeng Claudia Pappas Xiangjie Sun Paul J Carney Julie M Villanueva James Stevens Jacqueline M Katz Terrence M Tumpey
Affiliations 1 institutions
  1. Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.

Abstract

On 29 March 2013, the Chinese Center for Disease Control and Prevention confirmed the first reported case of human infection with an avian influenza A(H7N9) virus. The recent human infections with H7N9 virus, totalling over 130 cases with 39 fatalities to date, have been characterized by severe pulmonary disease and acute respiratory distress syndrome (ARDS). This is concerning because H7 viruses have typically been associated with ocular disease in humans, rather than severe respiratory disease. This recent outbreak underscores the need to better understand the pathogenesis and transmission of these viruses in mammals. Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals. Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus. Moreover, the H7N9 viruses showed greater infectivity and lethality in mice compared to genetically related H7N9 and H9N2 viruses. The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets. The lack of efficient respiratory droplet transmission was corroborated by low receptor-binding specificity for human-like α2,6-linked sialosides. Our results indicate that H7N9 viruses have the capacity for efficient replication in mammals and human airway cells and highlight the need for continued public health surveillance of this emerging virus.

Supporting text Virus Host Location
Animals 1948 Cell Line 158 Cell Polarity 1 Disease Models, Animal 77 Epithelial Cells 27 Female 289 Ferrets 79 Humans 1440 Influenza A virus 186 Influenza A Virus, H3N2 Subtype 48 Influenza A Virus, H9N2 Subtype 71 Influenza, Human 286 Madin Darby Canine Kidney Cells 36 Male 224 Mice 253 Mice, Inbred BALB C 73 Orthomyxoviridae Infections 228 Polysaccharides 31 Receptors, Virus 204 Respiratory System 21 Substrate Specificity 3 Virus Replication 191

Evidence records

5 total
Zoonotic Surveillance
2 records · 1 evidence types
Evidence type
2 records
OVE1508
Key finding

The A/Anhui/1/2013 (H7N9) virus was isolated from a fatal human case prior to experimental infection studies.

Virus
Host
Location
Not specified
Supporting text

Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals.

Sample type
clinical sample
OVE1509
Key finding

The A/Shanghai/1/2013 (H7N9) virus was isolated from a fatal human case prior to experimental infection studies.

Virus
Host
Location
Not specified
Supporting text

Here we assess the ability of A/Anhui/1/2013 and A/Shanghai/1/2013 (H7N9) viruses, isolated from fatal human cases, to cause disease in mice and ferrets and to transmit to naive animals.

Sample type
clinical sample
Experimental Infection
3 records · 2 evidence types
Evidence type
2 records
OVE1503
Key finding

A/Anhui/1/2013 (H7N9) replicated to high titres in human airway epithelial cells and ferret respiratory tract compared to a seasonal H3N2 virus.

Virus
Host
Location
Not specified
Supporting text

Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus.

Method
in vitro replication assay | animal infection study | viral titre quantification
Sample type
respiratory tract
Experimental system
human airway epithelial cell culture and ferret infection model
OVE1504
Key finding

A/Shanghai/1/2013 (H7N9) replicated to high titres in human airway epithelial cells and ferret respiratory tract compared to a seasonal H3N2 virus.

Virus
Host
Location
Not specified
Supporting text

Both H7N9 viruses replicated to higher titre in human airway epithelial cells and in the respiratory tract of ferrets compared to a seasonal H3N2 virus.

Method
in vitro replication assay | animal infection study | viral titre quantification
Sample type
respiratory tract
Experimental system
human airway epithelial cell culture and ferret infection model
Evidence type
1 records
OVE1505
Key finding

H7N9 viruses were transmitted between ferrets by direct contact but not efficiently by respiratory droplets.

Virus
Host
Location
Not specified
Supporting text

The H7N9 viruses were readily transmitted to naive ferrets through direct contact but, unlike the seasonal H3N2 virus, did not transmit readily by respiratory droplets.

Method
animal transmission model | contact exposure | aerosol transmission assessment
Experimental system
ferret contact and respiratory droplet transmission model