Characterization of a human H9N2 influenza virus isolated in Hong Kong.

T Saito1 W Lim T Suzuki Y Suzuki H Kida S I Nishimura M Tashiro
Affiliations 1 institutions
  1. Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan. [email protected]

Abstract

Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in 1999. Isolation of influenza viruses with a novel subtype of the hemagglutinin (HA) drew attention of health care authorities worldwide from the view of pandemic preparedness. Sequence analysis of the HA genes reveals that HA of A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97 (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1) viruses. Phylogenetic and antigenic analyses demonstrated the diversity among H9 HA. A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian hamsters, suggesting that the virus can replicate efficiently in mammalian hosts. We developed a whole virion test vaccine with a formalin-inactivated egg-grown HK1073. Intraperitoneal administration of the vaccine twice to hamsters conferred a complete protection against challenge infection by the MDCK cell-grown homologous virus. Receptor specificity of HK1073 appeared different from that of other avian influenza viruses of H9 subtype which recognize preferentially alpha-2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers. These data suggested that HK1073 had acquired a broader host range, including humans. Together with data so far available, the present study suggested that isolation of the H9 influenza viruses from humans requires precaution against the emergence of a novel human influenza.

Supporting text Virus Host Location
Influenza A Virus, H9N2 Subtype 71 Animals 1948 Antigens, Viral 49 Asia 13 Cattle 126 Cells, Cultured 26 Chick Embryo 20 Child 42 Cricetinae 41 Dogs 176 Europe 27 Female 289 Glycoconjugates 2 Guinea Pigs 21 Hemagglutination Tests 8 Hemagglutination, Viral 1 Hemagglutinin Glycoproteins, Influenza Virus 180 Hong Kong 21 Horses 52 Humans 1440 Influenza A virus 186 Influenza Vaccines 20 Influenza, Human 286 Lung 65

Evidence records

6 total
Zoonotic Surveillance
1 records · 1 evidence types
Evidence type
1 records
OVE102
Key finding

Two H9N2 influenza viruses were successfully isolated from human clinical samples in Hong Kong in 1999.

Virus
Host
Location
Not specified
Supporting text

Two H9N2 viruses were isolated, for the first time, from humans in Hong Kong in 1999.

Sample type
human clinical samples
Experimental Infection
1 records · 1 evidence types
Evidence type
1 records
OVE105
Key finding

The human H9N2 influenza virus A/Hong Kong/1073/99 caused a respiratory infection in experimentally infected Syrian hamsters.

Virus
Host
Location
Not specified
Supporting text

A/Hong Kong/1073/99 was shown to cause a respiratory infection in Syrian hamsters, suggesting that the virus can replicate efficiently in mammalian hosts.

Method
experimental infection of hamsters with A/Hong Kong/1073/99 | observation of clinical respiratory signs
Experimental system
Syrian hamster infection model
Functional Mechanism
2 records · 2 evidence types
Evidence type
1 records
OVE106
Key finding

The human H9N2 influenza virus HK1073 binds both alpha-2,3 and alpha-2,6 linked sialic acid receptors.

Virus
Host
Location
Not specified
Supporting text

Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers.

Method
hemagglutination inhibition assay
Receptors
alpha-2,3 linked sialic acid | alpha-2,6 linked sialic acid
Evidence type
1 records
OVE107
Key finding

The H9N2 influenza virus strain A/Hong Kong/1073/99 (HK1073) exhibited altered receptor binding specificity recognizing both α2,3- and α2,6-linked sialic acids, indicating molecular adaptation enabling broader host range including humans.

Virus
Host
Not specified
Location
Not specified
Supporting text

Receptor specificity of HK1073 appeared different from that of other avian influenza viruses of H9 subtype which recognize preferentially alpha-2,3 linked sialic acid. Hemagglutination of HK1073 with guinea pig erythrocytes was inhibited by both alpha-2,3 and alpha-2,6 linked sialic acid containing polymers. These data suggested that HK1073 had acquired a broader host range, including humans.

Genes or proteins
hemagglutinin (HA)
Receptors
α2,3-linked sialic acid | α2,6-linked sialic acid
Mechanism types
receptor binding | host-range expansion
Genomic Evolution
2 records · 1 evidence types
Evidence type
2 records
OVE103
Key finding

Phylogenetic analysis showed that the HA gene of the human A/Hong Kong/1073/99 (H9N2) virus is most closely related to that of quail A/quail/HK/G1/97 (H9N2), which carries internal genes similar to H5N1 viruses from Hong Kong/97.

Virus
Host
Location
Not specified
Supporting text

Sequence analysis of the HA genes reveals that HA of A/Hong Kong/1073/99 (H9N2) is most closely related to that of A/quail/HK/G1/97 (H9N2) that contains the internal genes similar to those of Hong Kong/97 (H5N1) viruses.

Genes or proteins
HA gene | internal genes
Analysis methods
sequence analysis | phylogenetic analysis
OVE104
Key finding

Phylogenetic and antigenic analyses demonstrated genetic diversity among H9 hemagglutinin sequences.

Virus
Host
Not specified
Location
Not specified
Supporting text

Phylogenetic and antigenic analyses demonstrated the diversity among H9 HA.

Genes or proteins
HA
Analysis methods
phylogenetic analysis | antigenic analysis