Influenza Epidemics


Influenza viruses can cause epidemics or pandemics (worldwide epidemics), during which acute febrile respiratory disease spreads rapidly among all age groups, accompanied by excess hospitalisation and death. Here, we describe the recorded influenza virus pandemics, including the most recent pandemic that was caused in 2009 by a novel virus of the H1N1 subtype. Influenza virus replication and adaptation to new hosts account for much of the evolutionary success of these viruses. We review the viral proteins that are known to affect host range and pathogenicity (i.e. the haemagglutinin protein HA, the neuraminidase protein NA, the polymerase protein PB2, the nonstructural protein NS1 and the PB1‐F2 protein). We also discuss the clinical features of influenza virus infections, influenza virus immunology and influenza virus control, including antiviral treatment and vaccination.

Key Concepts

  • Influenza A viruses cause annual epidemics that result from point mutations in the surface glycoprotein(s) HA (and NA) (antigenic drift).
  • At random intervals, influenza pandemics are caused by viruses that introduce HA proteins into the human population against which most humans lack immunity.
  • Influenza A viruses evolve through reassortment and point mutations.
  • Aquatic birds are the natural reservoir of influenza A viruses.
  • Influenza A viruses can be transmitted among species, despite host range restriction factors.
  • The HA protein is the major protective antigen and an important determinant of host range and pathogenicity.
  • The PB2, NS1 and PB1‐F2 proteins are also important determinants of pathogenicity.
  • Avian H5N1 and H7N9 viruses sporadically infect humans and cause severe respiratory infections with high case fatality rates; currently, these viruses do not transmit efficiently among humans.
  • For human influenza viruses, inactivated and live attenuated vaccines are available.
  • Three classes of antiviral compounds (ion channel, neuraminidase and polymerase inhibitors) exist: resistance to ion channel inhibitors is now widespread among circulating H1N1 and H3N2 influenza viruses; most human influenza viruses, as well as most avian H5N1 and H7N9 viruses, are sensitive to neuraminidase inhibitors, although viruses with resistance to neuraminidase inhibitors have been reported. Resistance to the recently approved polymerase inhibitor has not been reported yet.

Keywords: flu; pandemic; pandemic 2009 H1N1; genetic reassortment; antigenic drift; antigenic shift; interspecies transmission; avian influenza; bird flu; Spanish influenza, H5N1, H7N9

Figure 1. Genesis of pandemic 2009 H1N1 viruses. The NA and M genes were derived from an Eurasian avian‐like swine virus (yellow). The remaining six genes were derived from triple reassortant swine viruses that possessed genes originating from classical H1N1 swine (red), North American avian (blue) and human H3N2 (green) viruses. Reproduced from Neumann et al. 2009 © Nature Publishing Group.
Figure 2. Genesis of H7N9 influenza viruses. Phylogenetic analyses suggest that the novel H7N9 viruses likely resulted from the reassortment of several avian influenza A viruses. The H7N9 virus HA gene may have originated from avian H7N3 viruses that recently circulated in ducks in Eastern China. The H7N9 virus NA gene shares the highest homology with the NA genes of avian H2N9 and H11N9 influenza viruses. The remaining six viral genes are likely derived from poultry H9N2 influenza viruses circulating in Eastern China. Adapted with permission from Watanabe et al., 2014 © Elsevier.


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Further Reading

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Webster RG, Hulse‐Post DJ, Sturm‐Ramirez KM, et al. (2007) Changing epidemiology and ecology of highly pathogenic avian H5N1 influenza viruses. Avian Diseases 51 (1 Suppl): 269–272.

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Neumann, Gabriele, and Kawaoka, Yoshihiro(May 2015) Influenza Epidemics. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002241.pub4]