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United States Department of Agriculture

Agricultural Research Service

Research Project: FUNCTIONAL GENOMIC APPROACHES FOR CONTROLLING DISEASES OF SWINE

Location: Animal Parasitic Diseases

Title: Quantitative analysis of Porcine Reproductive and Respiratory Syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach

Authors
item Islam, Z -
item Bishop, S -
item Savill, N -
item Rowland, R -
item Lunney, Joan
item Trible, B -
item Doeschl-Wilson, A -

Research conducted cooperatively with:
item

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 13, 2013
Publication Date: December 17, 2013
Citation: Islam, Z.U., Bishop, S.C., Savill, N.J., Rowland, R.R., Lunney, J.K., Trible, B., Doeschl-Wilson, A.B. 2013. Quantitative analysis of Porcine Reproductive and Respiratory Syndrome (PRRS) viremia profiles from experimental infection: a statistical modelling approach. PLoS One. 8:e83567.

Interpretive Summary: Porcine reproductive and respiratory syndrome is the most economically significant viral disease facing the global swine industry, causing $642M/year losses to US pig producers. Profiles of serum viremia from PRRS virus challenged pigs reflect the severity and progression of the infection within the host and provide crucial information for subsequent control measures. This study sought a suitable mathematical description of all serum viremia profiles with biologically meaningful parameters. We established that the broad spectrum of viremia trends could be adequately represented by either the uni- or biphasic Wood's functions. Three viremic categories emerged: cleared, persistent and rebound. This analysis enabled us to establish a convenient biological interpretation of the model parameters estimates and to quantify inter-host variation that can now be further analyzed based on the genomic data on each pig. Persistent profiles were distinguishable within the first 21 days of infection, but it was not possible to predict when viremia would rebound. Analysis of the neutralizing antibody data indicated that there was a ubiquitous, strong response to the homologous PRRS challenge virus, but high variability in the reactivity with other, heterologous viruses, thus complicating interpretation of cross-protection. Persistent pigs were found to have a significantly higher cross-protectivity than pigs that either cleared viremia or experienced rebound. Overall our study provides novel insights into the nature and degree of variation of the pig's response to infection as well as new informative traits for subsequent genomic and modelling studies. This information will be useful to veterinarians, virologists, swine producers, and mathematical biologists.

Technical Abstract: Porcine reproductive and respiratory syndrome (PRRS) is the most economically significant viral disease facing the global swine industry. Viremia profiles of PRRS virus challenged pigs reflect the severity and progression of the infection within the host and provide crucial information for subsequent control measures. In this study we analyse the largest longitudinal PRRS viremia dataset from an in-vivo experiment. The primary objective was to provide a suitable mathematical description of all viremia profiles with biologically meaningful parameters for quantitative analysis of profile characteristics. The Wood's function, a gamma-type function, and a biphasic extended Wood's function were fit to the individual profiles using Bayesian inference with a likelihood framework. Using maximum likelihood inference and numerous fit criteria, we established that the broad spectrum of viremia trends could be adequately represented by either the uni- or biphasic Wood's functions. Three viremic categories emerged: cleared (uni-modal and below detection within 42 days post infection(dpi)), persistent (transient experimental persistence over 42dpi) and rebound (biphasic within 42dpi). The convenient biological interpretation of the model parameters estimates, allowed us not only to quantify inter-host variation, but also to establish common viremia curve characteristics and their predictability. Statistical analysis of the profile characteristics revealed that persistent profiles were distinguishable already within the first 21dpi, whereas it is not possible to predict the onset of viremia rebound. Analysis of the neutralizing antibody(nAb) data indicated that there was a ubiquitous strong response to the homologous PRRSV challenge, but high variability in the range of cross-protection of the nAbs. Persistent pigs were found to have a significantly higher nAb cross-protectivity than pigs that either cleared viremia or experienced rebound within 42dpi. Our study provides novel insights into the nature and degree of variation of hosts' responses to infection as well as new informative traits for subsequent genomic and modelling studies.

Last Modified: 12/20/2014
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