Journal article
Varying Inoculum Dose to Assess the Roles of the Immune Response and Target Cell Depletion by the Pathogen in Control of Acute Viral Infections
Bulletin of mathematical biology, Vol.82(3), pp.35-35
03/03/2020
DOI: 10.1007/s11538-020-00711-4
PMID: 32125535
Abstract
It is difficult to determine whether an immune response or target cell depletion by the infectious agent is most responsible for the control of acute primary infection. Both mechanisms can explain the basic dynamics of an acute infection-exponential growth of the pathogen followed by control and clearance-and can also be represented by many different differential equation models. Consequently, traditional model comparison techniques using time series data can be ambiguous or inconclusive. We propose that varying the inoculum dose and measuring the subsequent infectious load can rule out target cell depletion by the pathogen as the main control mechanism. Infectious load can be any measure that is proportional to the number of infected cells, such as viraemia. We show that a twofold or greater change in infectious load is unlikely when target cell depletion controls infection, regardless of the model details. Analyzing previously published data from mice infected with influenza, we find the proportion of lung epithelial cells infected was 21-fold greater (95% confidence interval 14-32) in the highest dose group than in the lowest. This provides evidence in favor of an alternative to target cell depletion, such as innate immunity, in controlling influenza infections in this experimental system. Data from other experimental animal models of acute primary infection have a similar pattern.
Details
- Title: Subtitle
- Varying Inoculum Dose to Assess the Roles of the Immune Response and Target Cell Depletion by the Pathogen in Control of Acute Viral Infections
- Creators
- James R Moore - Fred Hutch Cancer CenterHasan Ahmed - Emory UniversityBalaji Manicassamy - University of IowaAdolfo Garcia-Sastre - Icahn School of Medicine at Mount SinaiAndreas Handel - University of GeorgiaRustom Antia - Emory University
- Resource Type
- Journal article
- Publication Details
- Bulletin of mathematical biology, Vol.82(3), pp.35-35
- DOI
- 10.1007/s11538-020-00711-4
- PMID
- 32125535
- ISSN
- 0092-8240
- eISSN
- 1522-9602
- Grant note
- R01AI110720 / NIH HHS U19AI11789102 / NIH HHS U54GM111274 / NIH HHS
- Language
- English
- Date published
- 03/03/2020
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297437102771
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