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Abstract

Breathing with Birds


Recently, spread of an avian flu virus has thrown public health worldwide into panic. Historically, pandemic influenza viruses pose a significant threat to humans. 1 In the twentieth century, three influenza viruses emerged that caused major pandemics: the 1918 Spanish flu virus (killed an estimated 20 to 50 million people worldwide), the 1957 Asian flu virus, and the 1968 Hong Kong flu virus (both of which killed between 0.5 and 1 million people in the United States alone).The emergence of a new threat led scientists Taubenberger et al. 2 to sequence and phylogenetically analyse the complete genome of the 1918 influenza virus. They assembled the sequences of the eight gene segments of the 1918 pandemic virus from RNA fragments obtained from paraffin block and frozen tissue of several victims of the 1918 virus. They report the entire gene sequence of the virus and show remarkable similarities between the polymerase genes of the influenza virus that caused the 1918 Spanish influenza pandemic and those of subsequent avian influenza viruses. Additionally, they confirm that the 1918 Spanish influenza virus was not a reassortant virus (like the 1957 and 1968 viruses) but rather was an entirely avian-like virus that became adapted to humans through mutation. This means that currently circulating, highly pathogenic avian influenza viruses could evolve into human pandemic viruses either through gene reassortment or through direct mutation of viral genes.Simultaneously, Tumpey et al. 3 successfully reconstructed the deadly 1918 pandemic virus in mice and showed that it kills mice faster than any other influenza virus so far tested. The purpose of this landmark experiment was to ‘understand more fully the virulence of this virus and possibly of other human influenza pandemic viruses.’ As the threat of the emergence of another pandemic virus is considered likely, characterization of the 1918 virus may help recognize the potential threat posed by new influenza virus strains, and direct us towards appropriate prophylactic and therapeutic countermeasures that will be needed to control pandemic viruses.The currently circulating avian H5N1 strain is genetically similar to the 1918 Spanish virus1. Russell and Webster1 believe that 'the substantial number of human cases caused by the H5N1 strain of avian influenza virus over the past two years (118 reported cases and 61 deaths), some clusters of probable human-to-human transmission, and the similarity to 1918 pandemic influenza virus all suggest that the only remaining trait for H5N1 to acquire to become a pandemic virus is efficient human transmissibility.' This poses a viable threat as the geographical range of migratory birds has increased and the H5N1 strain is already endemic in migratory birds. 1. Russell CJ, Webster RG. The Genesis of a Pandemic Influenza Virus. Cell. 2005; 368-71.2. Taubenberger JK, Reid AH, Lourens RM, Wang R, Jin G, Fanning TG. Characterization of the 1918 influenza virus polymerase genes. Nature 2005; 437: 889-93.3. Tumpey TM, Basler CF, Aguilar PV, Zeng H, Solo´rzano A, Swayne DE, Cox NJ, Katz JM, Taubenberger JK, Palese P, Garci ´a-Sastre, A. Characterization of the Reconstructed 1918 Spanish Influenza Pandemic Virus. Science 2005; 310: 77-80.