Abstract
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.
Highlights
The crucial genes are those encoding the two viral surface proteins hemagglutinin (H or HA) and neuraminidase (N or NA)
The influenza virus genome is organized in eight discrete segments and, if a single cell is infected simultaneously with a ‘human’ and an ‘avian’ virus, the segments can become re-packaged to give a novel variant that could, for instance, express completely new avian HA or NA types but whose other genes remain adapted to enable them to spread in people
The three viruses that circulated in people through the 20th century were H1N1, H2N2 and H3N2
Summary
Q&A: What do we know about influenza and what can we do about it? Peter C Doherty*,† and Stephen J Turner*. The resulting virus variants are 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. The influenza virus genome is organized in eight discrete segments and, if a single cell is infected simultaneously with a ‘human’ and an ‘avian’ virus, the segments can become re-packaged to give a novel variant that could, for instance, express completely new (to humans) avian HA or NA types but whose other genes remain adapted to enable them to spread in people. There is emerging evidence that elements of the three-component viral polymerase complex (PB1 and PB2) can influence transmissibility [4], though the underlying mechanism of host specificity in this case is not clear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
