Giuseppe
Emeritus
Dynamics of Infection and Pathology in Influenza. (J Virol., abstract, edited)
7. J Virol. 2010 Feb 3. [Epub ahead of print]
Dynamics of Infection and Pathology in Influenza.
Saenz RA, Quinlivan M, Elton D, Macrae S, Blunden AS, Mumford JA, Daly JM, Digard P, Cullinane A, Grenfell BT, McCauley JW, Wood JL, Gog JR. - Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, UK; Virology Unit, Irish Equine Centre, Johnstown, Naas, Co. Kildare, Ireland; Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK; Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK; Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Department of Ecology and Evolutionary Biology, and Woodrow Wilson School, Eno Hall, Princeton University, Princeton NJ 08540, USA; Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA; Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
A key question in pandemic influenza is the relative role 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.
PMID: 20130053 [PubMed - as supplied by publisher]
-
------
7. J Virol. 2010 Feb 3. [Epub ahead of print]
Dynamics of Infection and Pathology in Influenza.
Saenz RA, Quinlivan M, Elton D, Macrae S, Blunden AS, Mumford JA, Daly JM, Digard P, Cullinane A, Grenfell BT, McCauley JW, Wood JL, Gog JR. - Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Wilberforce Road, Cambridge CB3 0WA, UK; Virology Unit, Irish Equine Centre, Johnstown, Naas, Co. Kildare, Ireland; Animal Health Trust, Lanwades Park, Kentford, Newmarket CB8 7UU, UK; Cambridge Infectious Diseases Consortium, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK; Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK; Department of Ecology and Evolutionary Biology, and Woodrow Wilson School, Eno Hall, Princeton University, Princeton NJ 08540, USA; Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA; Division of Virology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
A key question in pandemic influenza is the relative role 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.
PMID: 20130053 [PubMed - as supplied by publisher]
-
------