Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.

M Hatta¹ P Gao P Halfmann Y Kawaoka

Affiliations 1 institutions

Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53706, USA.

PMID11546875 DOI10.1126/science.1062882 Year2001 Journal Science (New York, N.Y.) Science Languageeng Statusppublish

Abstract

In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. When mice were infected with the human isolates, two virulence groups became apparent. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice. Moreover, high cleavability of the hemagglutinin glycoprotein was an essential requirement for lethal infection.

Supporting text Virus Host Location

Influenza A Virus, H5N1 Subtype 300 Amino Acid Sequence 128 Animals 1949 Birds 212 DNA, Recombinant 1 Hemagglutinin Glycoproteins, Influenza Virus 180 Hong Kong 21 Humans 1441 Influenza A virus 186 Influenza, Human 286 Lung 65 Mice 253 Mutation, Missense 26 Reassortant Viruses 103 RNA-Dependent RNA Polymerase 49 Viral Proteins 152 PB2 protein, Influenzavirus A 27

Evidence records

3 total

Transmission Evidence

1 records · 1 evidence types

Evidence type Spillover Event

1 records

OVE11436 Spillover Event

Key finding

H5N1 influenza A virus was transmitted from birds to humans in Hong Kong in 1997, causing fatal human cases.

Virus

Host

Location

Supporting text

In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected.

Method: virus isolation | clinical case investigation
Study design: epidemiological observation of spillover cases
Transmission direction: animal-to-human
Geographic raw: Hong Kong
Country inferred: CHN

Experimental Infection

1 records · 1 evidence types

Evidence type Pathogenicity Experiment

1 records

OVE11437 Pathogenicity Experiment

Key finding

Experimental infection of mice with human H5N1 influenza A virus isolates revealed two virulence groups differing in disease severity.

Virus

Host

Location

Supporting text

When mice were infected with the human isolates, two virulence groups became apparent.

Method: experimental infection | observation of clinical outcomes in mice
Experimental system: mouse infection model

Functional Mechanism

1 records · 1 evidence types

Evidence type Molecular Adaptation

1 records

OVE11438 Molecular Adaptation

Key finding

A mutation at position 627 in the PB2 protein of H5N1 influenza A virus increases virulence in mice.

Virus

Host

Location

Supporting text

In 1997, an H5N1 influenza A virus was transmitted from birds to humans in Hong Kong, killing 6 of the 18 people infected. Using reverse genetics, we showed that a mutation at position 627 in the PB2 protein influenced the outcome of infection in mice.

Genes or proteins: PB2 protein
Mutations: mutation at position 627
Mechanism types: virulence adaptation | replication adaptation