Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus

doi:10.1016/S0140-6736(97)11212-0

The Lancet

Volume 351, Issue 9101, 14 February 1998, Pages 472-477

https://doi.org/10.1016/S0140-6736(97)11212-0 Get rights and content

Summary

Background

In May, 1997, a 3-year-old boy in Hong Kong was admitted to the hospital and subsequently died from influenza pneumonia, acute respiratory distress syndrome, Reye's syndrome, multiorgan failure, and disseminated intravascular coagulation. An influenza A H5N1 virus was isolated from a tracheal aspirate of the boy. Preceding this incident, avian influenza outbreaks of high mortality were reported from three chicken farms in Hong Kong, and the virus involved was also found to be of the H5 subtype.

Methods

We carried out an antigenic and molecular comparison of the influenza A H5N1 virus isolated from the boy with one of the viruses isolated from outbreaks of avian influenza by haemagglutination-inhibition and neuraminidase-inhibition assays and nucleotide sequence analysis.

Findings

Differences were observed in the antigenic reactivities of the viruses by the haemagglutination-inhibition assay. However, nucleotide sequence analysis of all gene segments revealed that the human virus A/Hong Kong/156/97 was genetically closely related to the avian A/chicken/Hong Kong/258/97.

Interpretation

Although direct contact between the sick child and affected chickens has not been established, our results suggest transmission of the virus from infected chickens to the child without another intermediate mammalian host acting as a “mixing vessel”. This event illustrates the importance of intensive global influenza surveillance.

Introduction

It is nearly 30 years since the last human influenza pandemic occurred, the Hong Kong pandemic of 1968. The influenza A H3N2 virus that was then introduced into the human population was shown to carry a new haemagglutinin, the major surface glycoprotein of the influenza virus. The influenza A H2N2 virus responsible for the previous 1957 pandemic carried new surface glycoproteins haemagglutinin and neuraminidase. Phylogenetic studies revealed that these newly emerging glycoproteins originated from avian viruses and had entered the human population after reassortment with human influenza virus strains.1, 2, 3

However, the virus involved in the most devastating pandemic known to have occurred in human beings—the influenza A H1N1 virus of the 1918 pandemic, which killed over 20 million people worldwide—may have entered the human population without a reassortment event.4, 5 To date, as many as 15 different haemagglutinins and nine neuraminidases have been identified in avian species,6, 7 providing an extensive reservoir of influenza viruses that could be transmitted to other species.

In May, 1997, an influenza virus was isolated from a tracheal aspirate of a 3-year-old boy in Hong Kong, who died a few days after admission to hospital.⁸ The child died from influenza pneumonia, acute respiratory distress syndrome (ARDS), Reye's syndrome, multiorgan failure, and disseminated intravascular coagulation, and had no known underlying diseases before admission. The virus could not be characterised in the haemagglutination-inhibition (HI) test with post-infection ferret antisera raised against recent human and swine influenza viruses. Further analysis revealed the virus to be an influenza A H5N1, a subtype previously not detected in human beings.⁸ Here we present the genetic characterisation of this first human influenza A H5N1 isolate and the comparison with an influenza A H5N1 virus isolated from outbreaks of avian influenza in chickens in Hong Kong that preceded the human infection.

Section snippets

Methods

The human virus A/Hong Kong/156/97 (H5N1) was propagated on Madin-Darby canine kidney (MDCK) cells.⁸ Avian influenza outbreaks occurred in Hong Kong over the period late March to early May, 1997. Three chicken farms were separately affected and the overall mortality rate for the 6800 chickens exceeded 70%. On two of the farms the rate was close to 100%. From these three farms, avian influenza viruses of the H5 subtype were isolated by inoculation of pooled organ material of dead chickens into

Results

An HI assay was done with the HK97 virus against a panel of 23 hyperimmune sera directed to variants of influenza viruses of 14 haemagglutinin subtypes (H1-H14). The anti-H5 serum, raised by immunisation with A/tern/South Africa/63 (H5N3), inhibited haemagglutination of the HK97 virus with turkey erythrocytes up to a dilution of 1/2560. None of the other sera inhibited haemagglutination, indicating that the isolate was of the H5 subtype. Oligonucleotide primers were selected on the basis of

Discussion

We have shown clearly the genetic similarity of HK97, the first human influenza virus isolate of the H5N1 subtype, and a virus that was isolated in outbreaks of avian influenza in Hong Kong that preceded human infection. Only three aminoacid differences were observed in the HA1 part of the H5 haemagglutinin, none of which affected directly the receptor-binding site. Therefore, the H5 haemagglutinin of HK97 probably had not acquired aminoacid mutations that have been associated with binding to

References (33)

RG Webster et al.
Studies on the origin of pandemic influenza. Antigenic analysis of A 2 influenza viruses isolated before and after appearance of Hong Kong influenza using antisera to the isolated hemagglutinin subunits
Virology
(1972)
C Scholtissek et al.
On the origin of the human influenza virus subtypes H2N2 and H3N2
Virology
(1978)
C Röhm et al.
Characterization of a novel influenza hemagglutinin, H15: criteria for determination of Influenza A subtypes
Virology
(1996)
Y Kawaoka et al.
Molecular analyses of the hemagglutinin genes of H5 influenza viruses: origin of a virulent turkey strain
Virology
(1987)
E Nobusawa et al.
Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of hemagglutinins of influenza A viruses
Virology
(1991)
FX Bosch et al.
Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of avian influenza virus
Virology
(1981)
T Saito et al.
Emergence of a potentially pathogenic H5N2 influenza virus in chickens
Virology
(1994)
GN Rogers et al.
Receptor determinants of human and animal influenza virus isolates: differences in receptor specificity of the H3 hemagglutinin based on species of origin
Virology
(1983)
RJ Connor et al.
Receptor specificity in human, avian and equine H2 and H3 influenza virus isolates
Virology
(1994)
J Kurtz et al.
Avian influenza virus isolated from a woman with conjunctivitis
Lancet
(1996)

MR Castrucci et al.

Genetic reassortment between avian and human influenza A viruses in Italian pigs

Virology

(1993)

ECJ Claas et al.

Infection of children with avian-human reassortant influenza virus from pigs in Europe

Virology

(1994)

KF Shortridge

The next pandemic influenza virus?

Lancet

(1995)

Y Kawaoka et al.

Avian-to-human transmission of the PB1 of influenza A viruses in the 1957 and 1968 pandemics

J Virol

(1989)

OT Gorman et al.

Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses

J Virol

(1991)

JK Taubenberger et al.

Initial characterization of the 1918 "Spanish" influenza virus

Science

(1997)

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ArticlesHuman influenza A H5N1 virus related to a highly pathogenic avian influenza virus

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Virology

Virology

Virology

Virology

Virology

Virology

Virology

Virology

Virology

Lancet

Virology

Virology

Lancet

Avian-to-human transmission of the PB1 of influenza A viruses in the 1957 and 1968 pandemics

J Virol

Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses

J Virol

Initial characterization of the 1918 "Spanish" influenza virus

Science

Articles
Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus