Reducing Uncertainty in Within-Host Parameter Estimates of Influenza Infection by Measuring Both Infectious and Total Viral Load
نویسندگان
چکیده
For in vivo studies of influenza dynamics where within-host measurements are fit with a mathematical model, infectivity assays (e.g. 50% tissue culture infectious dose; TCID50) are often used to estimate the infectious virion concentration over time. Less frequently, measurements of the total (infectious and non-infectious) viral particle concentration (obtained using real-time reverse transcription-polymerase chain reaction; rRT-PCR) have been used as an alternative to infectivity assays. We investigated the degree to which measuring both infectious (via TCID50) and total (via rRT-PCR) viral load allows within-host model parameters to be estimated with greater consistency and reduced uncertainty, compared with fitting to TCID50 data alone. We applied our models to viral load data from an experimental ferret infection study. Best-fit parameter estimates for the "dual-measurement" model are similar to those from the TCID50-only model, with greater consistency in best-fit estimates across different experiments, as well as reduced uncertainty in some parameter estimates. Our results also highlight how variation in TCID50 assay sensitivity and calibration may hinder model interpretation, as some parameter estimates systematically vary with known uncontrolled variations in the assay. Our techniques may aid in drawing stronger quantitative inferences from in vivo studies of influenza virus dynamics.
منابع مشابه
A phase II study of DAS181, a novel host directed antiviral for the treatment of influenza infection.
BACKGROUND DAS181, a novel host-directed antiviral in development for influenza treatment, was assessed in this phase II clinical trial. METHODS This study was a double-blind, placebo-controlled phase II clinical trial assessing influenza viral load and patient safety in otherwise healthy influenza-infected participants. Participants were randomized to a single-dose, multiple-dose, or placebo...
متن کاملAnti-influenza Activity of a Novel Polyoxometalate Derivative (POM-4960)
There are many effective chemothereutic agents used in influenza disease which some of them inhibit virus replication by interfering with FluV (influenza virus) viral binding or its penetration into cell membrane. A series of polyoxometalates compounds such as POM-523 and PM-504 have been synthesized and have showed inhibitory effects on viruses. In this study we examined anti influenza activit...
متن کاملCaspase Cleavage Motifs of Influenza Subtypes Proteins: Alternations May Switch Viral Pathogenicity
Background and Aims: The caspases are unique proteases that mediate the host cell apoptosis during viral infection. In this study, we identified the caspase cleavage motifs of H5N1 and H9N2 influenza viruses isolated during 1998-2012. Materials and Methods: Amino acid sequences of the eleven proteins encoded by the viruses as the caspase substrates downloaded from NCBI. The caspase cleavage mot...
متن کاملPoliovirus Particles do not Form in Preinfected Cells with Reovirus
Background and Aims: Inhibition of viral growth in coinfected cells with two different viruses has been described. This phenomenon known as viral interference can occur in several virus host systems such as interference of enterovirus infection on poliovirus vaccine strains. In this study we superinfected reovirus infected HeLa cells with poliovirus to determine if poliovirus can replicate in s...
متن کامل