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Literature detail

Inefficient transmission of H5N1 influenza viruses in a ferret contact model.

Hui-Ling Yen1 Aleksandr S Lipatov Natalia A Ilyushina Elena A Govorkova John Franks Neziha Yilmaz Alan Douglas Alan Hay Scott Krauss Jerold E Rehg Erich Hoffmann Robert G Webster
Affiliations 1 institutions
  1. Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
PMID 17459930 2007 J Virol eng ppublish
PubMed DOI Browse context

Article

Publication summary

The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess "avian-like" alpha2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 10(3) 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for "human-like" alpha2,6-linked SA receptors in addition to their affinity for alpha2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

Disease Models, Animal Animals Disease Outbreaks Ferrets Humans Influenza A Virus, H5N1 Subtype Nasal Cavity Orthomyxoviridae Infections Species Specificity Virus Shedding

Structured evidence records

Evidence records

4 total
Cross Species Transmission 1 records
Cross Species Transmission Extraction confidence 0.90
Key finding

A/Vietnam/JP36-2/05 H5N1 virus transmitted inefficiently between ferrets in direct contact.

Virus
IAV H5N1
Location
Not specified
Supporting text

In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together.

Method
experimental infection; contact transmission model; virus detection; serology
Study design
animal experiment
Transmission direction
animal-to-animal
Host Range Experiment 1 records
Host Range Experiment Extraction confidence 1.00
Key finding

Experimental infection of ferrets with human H5N1 influenza virus isolates showed inefficient or limited transmission to contact ferrets, demonstrating restricted mammalian host-to-host spread.

Virus
IAV H5N1
Location
Not specified
Supporting text

To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected, while limited virus shedding and infection were observed among some contact ferrets.

Method
experimental infection; contact transmission study; virus detection
Sample type
nasal washes
Experimental system
in vivo animal experiment
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.80
Key finding

Differences in H5N1 influenza virus receptor binding specificity between avian-like alpha2,3-linked and human-like alpha2,6-linked sialic acid receptors were associated with altered pathogenicity but limited mammalian transmissibility, indicating incomplete molecular adaptation for efficient spread.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess 'avian-like' alpha2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets, whereas A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for 'human-like' alpha2,6-linked SA receptors in addition to alpha2,3-linked receptors, caused mild clinical symptoms. Despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

Genes or proteins
hemagglutinin
Receptors
alpha2,3-linked sialic acid receptor; alpha2,6-linked sialic acid receptor
Mechanism types
receptor_binding; pathogenicity; host_range_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

H5N1 viruses differed in receptor binding specificity: A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 had avian-like α2,3-linked sialic acid receptor usage, and A/Hong Kong/213/03 and A/Turkey/65-596/06 had dual affinity for α2,3- and α2,6-linked sialic acid receptors, influencing their pathogenicity and transmissibility in ferrets.

Virus
IAV H5N1
Location
Not specified
Supporting text

The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess 'avian-like' alpha2,3-linked sialic acid receptor specificity, caused neurological symptoms and death in ferrets, whereas A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for 'human-like' alpha2,6-linked SA receptors in addition to alpha2,3-linked receptors, caused mild clinical symptoms.

Method
synthetic sialosaccharide binding assay
Receptors
sialic acid (α2,3-linked and α2,6-linked receptors)