Lethal synergism between influenza virus and Streptococcus pneumoniae: characterization of a mouse model and the role of platelet-activating factor receptor

J Infect Dis. 2002 Aug 1;186(3):341-50. doi: 10.1086/341462. Epub 2002 Jul 10.


A lethal synergism exists between influenza virus and pneumococcus, which likely accounts for excess mortality from secondary bacterial pneumonia during influenza epidemics. Characterization of a mouse model of synergy revealed that influenza infection preceding pneumococcal challenge primed for pneumonia and led to 100% mortality. This effect was specific for viral infection preceding bacterial infection, because reversal of the order of administration led to protection from influenza and improved survival. The hypothesis that influenza up-regulates the platelet-activating factor receptor (PAFr) and thereby potentiates pneumococcal adherence and invasion in the lung was examined in the model. Groups of mice receiving CV-6209, a competitive antagonist of PAFr, had survival rates similar to those of control mice, and lung and blood bacterial titers increased during PAFr inhibition. These data suggest that PAFr-independent pathways are operative in the model, prompting further study of receptor interactions during pneumonia and bacteremia. The model of lethal synergism will be a useful tool for exploring this and other mechanisms underlying viral-bacterial interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Lung / microbiology
  • Lung / pathology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae / metabolism
  • Orthomyxoviridae / pathogenicity*
  • Orthomyxoviridae Infections / complications*
  • Orthomyxoviridae Infections / metabolism
  • Platelet Membrane Glycoproteins / metabolism
  • Platelet Membrane Glycoproteins / physiology*
  • Pneumonia, Pneumococcal / complications*
  • Pneumonia, Pneumococcal / metabolism
  • Pyridinium Compounds / pharmacology
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*
  • Streptococcus pneumoniae / metabolism
  • Streptococcus pneumoniae / pathogenicity*


  • Platelet Membrane Glycoproteins
  • Pyridinium Compounds
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • platelet activating factor receptor
  • CV 6209