Human influenza A H 5 N 1 virus related to a highly pathogenic avian influenza virus

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. 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. To date, as many as 15 different haemagglutinins and nine neuraminidases have been identified in avian species, 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. 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 postinfection 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. 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.