Avian influenza viruses and influenza in humans

Influenza-A viruses cause natural infections of humans, some other mammals and birds. Few of the 15 haemagglutinin and 9 neuraminidase subtype combinations have been isolated from mammals, but all subtypes have been isolated from birds. There are enormous pools of influenza-A viruses in wild birds, especially migratory waterfowl. In the 20th century there were 4 pandemics of influenza due to the emergence of antigenically different strains in humans: 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1). The RNA of influenza-A viruses is segmented into 8 distinct genes and as a result genetic reassortment can occur in mixed infections with different viruses. The 1957 and 1968 pandemic viruses differed from the preceding viruses in humans by the substitution of some genes that came from avian viruses, indicating that pandemic viruses may arise by genetic reassortment of viruses of human and avian origin. In poultry some influenza-A viruses cause highly pathogenic avian influenza [HPAI], with 100% mortality in infected flocks. The virulence of HPAI viruses is related to the presence of multiple basic amino acids at the precursor HA0 cleavage site, which enables it to be cleaved, and the virus rendered infectious, by a ubiquitous protease (e.g. furin), causing a systemic infection, instead of being restricted to cleavage by trypsin-like proteases. Humans also have furin, but none of the pandemic viruses have had HA0 cleavage sites with multiple basic amino acids. Up to 1995 there had been only three reports of avian influenza viruses infecting humans, in 1959, 1977 and 1981. All three viruses were H7N7 and two of these infections were the result of laboratory accidents. However, since 1996 there have been regular reports of natural infections of humans with avian influenza viruses. Isolations of avian influenza viruses from humans in England in 1996 [H7N7], Hong Kong in 1997 [H5N1] and 1999 [H9N2] caused concern that a new influenza pandemic could begin. The H5N1 virus was especially alarming, as it possessed multiple basic amino acids at the HA0 cleavage site and 6/18 of the people infected died. In 2003 further human infections with H5N1 virus were reported in Hong Kong with two associated deaths and in The Netherlands a total of 82 people were confirmed as infected with the H7N7 virus responsible for a series of HPAI outbreaks in poultry, one death was reported. Although these infections seem to have been limiting, with very little human to human transmission, they are a cause for alarm since, if people infected with an ‘avian’ virus were infected simultaneously with a Virology Department, Veterinary Laboratories Agency Weybridge, Addlestone, Surrey KT15 3NB, United Kingdom. E-mail: [email protected] Istituto Zooprofilattico Sperimentale delle Venezie, Viale dell’Università 10, 35020 Legnaro, Padova, Italy. E-mail: [email protected]