Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae

Jonathan Mccullers, Kimberly C. Bartmess

Research output: Contribution to journalArticle

258 Citations (Scopus)

Abstract

A lethal synergism exists between influenza virus and Streptococcus pneumoniae, accounting for excess mortality during influenza epidemics. Using a model of viral-bacterial synergism, we assessed the role that the influenza virus neuraminidase (NA) has in priming mice for pneumococcal infection. Administration of the selective NA inhibitor oseltamivir improved survival, independent of viral replication and morbidity from influenza. Both pathologic examination of the lungs and live imaging of pneumonic lesions, using a bioluminescent pneumococcus, suggested that the effect of NA inhibition was to limit the extent of pneumococcal pneumonia during early infection. Adherence assays and immunohistochemical staining for sialic acids in lungs from infected mice demonstrated that the influenza virus NA potentiates development of pneumonia by stripping sialic acid from the lung, thus exposing receptors for pneumococcal adherence. Selective NA inhibitors may be useful clinically to interrupt this novel mechanism of synergism and to prevent excess mortality from secondary bacterial pneumonia.

Original languageEnglish (US)
Pages (from-to)1000-1009
Number of pages10
JournalJournal of Infectious Diseases
Volume187
Issue number6
DOIs
StatePublished - Mar 15 2003
Externally publishedYes

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Neuraminidase
Streptococcus pneumoniae
Orthomyxoviridae
Lung
Human Influenza
Pneumococcal Pneumonia
Sialic Acids
Oseltamivir
Pneumococcal Infections
Bacterial Pneumonia
Mortality
N-Acetylneuraminic Acid
Pneumonia
Staining and Labeling
Morbidity
Infection

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Cite this

Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. / Mccullers, Jonathan; Bartmess, Kimberly C.

In: Journal of Infectious Diseases, Vol. 187, No. 6, 15.03.2003, p. 1000-1009.

Research output: Contribution to journalArticle

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