Editorial [Hot Topic: Influenza Virus Pathogenesis and Drug Targets (Guest Editor: Christopher F. Basler)]

While seasonal influenza, caused by influenza A viruses and influenza B viruses, continues to cause significant morbidity and mortality, pandemic influenza raises fears of a potentially catastrophic public health event. Two occurrences in particular have galvanized support for influenza virus research, particularly as it pertains to pandemics. The first was the identification of human cases, and particularly those resulting in human deaths, of avian influenza. Such cases were first recognized in Hong Kong in 1997, when 6 of 18 human cases of avian H5N1 influenza virus infections led to death. Despite the eradication of such viruses from the live bird markets of Hong Kong at the time, highly pathogenic avian influenza reemerged in poultry in 2004. Since 2004, H5N1 has spread from Asia, to Europe and to the Middle East and Africa. At least 327 human cases with 199 human deaths have occurred by infection from close human contact with avian species. This has raised fears of a human pandemic in which the avian-adapted H5N1 viruses either mutate to become adapted to humans or reassort their multiple genomic RNA segments with those of circulating human strains such that a virus with novel antigenicity and the capacity to efficiently spread from human to human becomes established in the human population. The second was the reconstruction of the 1918 pandemic influenza virus, a virus that killed an estimated 20-40 million people worldwide. Characterization of the fully reconstructed pandemic virus demonstrated that this was a virus with unique virulence characteristics, not typical of other human isolates. In addition to capturing the public imagination, the 1918 virus reconstruction opened up new opportunities to characterize the pathogenesis and transmission properties of highly virulent human influenza viruses. It is with this as a background that the components of this volume were conceived. The reviews that follow describe our current understanding of pandemic influenza, and focus on important new findings that have grown out of this emphasis on H5N1 and 1918 viruses. The goal of these reviews is to suggest how this new information may be employed to develop new anti-influenza virus strategies. Influenza viruses: Basic Biology and Current Antiviral Strategies (Basler): This review provides a brief overview of the biology of influenza A viruses with a particular emphasis on their molecular biology and basic epidemiology. A goal is to define the functions of the 11 known viral proteins, indicating their role in viral replication, and thereby highlight potential viral functions that might be targeted. Also discussed are the uses and limitations of the existing antivirals that target the M2 ion channel (amantadine and rimantadine) and that target the viral neuraminidase (NA) (oseltamivir and zanamavir). Reconstruction of the 1918 Pandemic Influenza Virus: How Revealing the Molecular Secrets of the Virus Responsible for the Worst Pandemic in Recorded History Can Guide Our Response to Future Influenza Pandemics (Perrone and Tumpey): Dr. Tumpey has been involved in the direct characterization of both H5N1 and 1918 influenza viruses. This article focuses on lessons learned from study of the 1918 pandemic virus and this information might be used to devise interventions for future pandemics. Pandemic Influenza: Preventing the emergence of novel strains and countermeasures to ameliorate its effects. (Solorzano, Song, Hickman and Perez): Dr. Perez reviews the role of influenza viruses that circulate in animal, primarily avian, reservoirs in the emergence of new human pandemic strains. Particular attention is paid to the ecology of avian influenza viruses, host range determinants and the potential role of other species as intermediate strains the may facilitate the reassortment of human and avian into pandemic strains. In this context, “intervention strategies” to prevent emergence of pandemic strains are discussed. Influenza Virus Transmission: Basic science and implications for the use of antiviral drugs during a pandemic (Lowen and Palese): Drs. Lowen and Palese review recently developed animal models that permit transmission of influenza viruses to be characterized. Both viral and host determinants of transmission are critical for the emergence of pandemic strains, for the persistence in humans of seasonal influenza and have important implications for antiviral strategies........