Dynamics of influenza virus infection and pathology

Roberto A. Saenz, Michelle Quinlivan, Debra Elton, Shona Macrae, Anthony S. Blunden, Jennifer A. Mumford, Janet M. Daly, Paul Digard, Ann Cullinane, Bryan T. Grenfell, John W. McCauley, James L.N. Wood, Julia R. Gog

Research output: Contribution to journalArticle

108 Scopus citations

Abstract

A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore how differences in the influence of viral proteins on interferon kinetics can account for the observed spectrum of virus shedding, immune response, and influenza pathology. In particular, induction of high levels of interferon ("cytokine storms"), coupled with evasion of its effects, could lead to severe pathology, as hypothesized for some fatal cases of influenza.

Original languageEnglish (US)
Pages (from-to)3974-3983
Number of pages10
JournalJournal of virology
Volume84
Issue number8
DOIs
StatePublished - Apr 2010

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Saenz, R. A., Quinlivan, M., Elton, D., Macrae, S., Blunden, A. S., Mumford, J. A., Daly, J. M., Digard, P., Cullinane, A., Grenfell, B. T., McCauley, J. W., Wood, J. L. N., & Gog, J. R. (2010). Dynamics of influenza virus infection and pathology. Journal of virology, 84(8), 3974-3983. https://doi.org/10.1128/JVI.02078-09