Q&A: What do we know about influenza and what can we do about it?

نویسندگان

  • Peter C Doherty
  • Stephen J Turner
چکیده

Influenza pandemics occur when human populations are infected by a variant virus to which a population has no prior immunity. What are the crucial varying genes? The crucial genes are those encoding the two viral surface proteins hemagglutinin (H or HA) and neuraminidase (N or NA). The influenza A viruses [1] that infect mammals like us replicate principally in the epithelial cells of the airways. The HA facilitates viral entry by binding to sialic acid residues on the epithelial cell surface, while the NA functions to cleave such attachments, and so release new virus particles, or virions, both from the cell and from the slimy mucous that protects the lung and trachea. The new virions are then free to spread the infection, both from cell to cell and to other susceptible individuals. Antibodies that bind to either the HA or the NA and block their function effectively prevent (or terminate) the infectious process and thus provide protective immunity. The anti-influenza drugs zanamivir and oselatamivir (Relenza and Tamiflu) operate by blocking the NA active site and, as this was first characterized by the structural analysis of NA-antibody complexes, are among the earliest examples of rational drug design. The variability of the HA and NA proteins is due to lack of proof reading by the viral polymerase that leads in turn to poor fidelity of genome copying and frequent occurrence of mutations. The resulting virus variants are then subjected to selective pressure by neutralizing (blocking) antibodies produced by immune individuals, leading to the emergence of so-called escape mutants that are not detected by antibodies against the original virus and cause annual, or biennial, ‘seasonal’ influenza outbreaks. Such a virus can spread across the USA within a single month.

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عنوان ژورنال:
  • Journal of Biology

دوره 8  شماره 

صفحات  -

تاریخ انتشار 2009