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Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections
Department of Statistics, Pennsylvania State University, University Park, PA 16802, USA
Department of Biology, Pennsylvania State University, University Park, PA 16802, USA
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA
These authors contributed equally to this paper.
* Author to whom correspondence should be addressed.
Received: 15 November 2010; in revised form: 12 December 2010 / Accepted: 13 December 2010 / Published: 22 December 2010
Abstract: The cell response to virus infection and virus perturbation of that response is dynamic and is reflected by changes in cell susceptibility to infection. In this study, we evaluated the response of human epithelial cells to sequential infections with human respiratory syncytial virus strains A2 and B to determine if a primary infection with one strain will impact the ability of cells to be infected with the second as a function of virus strain and time elapsed between the two exposures. Infected cells were visualized with fluorescent markers, and location of all cells in the tissue culture well were identified using imaging software. We employed tools from spatial statistics to investigate the likelihood of a cell being infected given its proximity to a cell infected with either the homologous or heterologous virus. We used point processes, K-functions, and simulation procedures designed to account for specific features of our data when assessing spatial associations. Our results suggest that intrinsic cell properties increase susceptibility of cells to infection, more so for RSV-B than for RSV-A. Further, we provide evidence that the primary infection can decrease susceptibility of cells to the heterologous challenge virus but only at the 16 h time point evaluated in this study. Our research effort highlights the merits of integrating empirical and statistical approaches to gain greater insight on in vitro dynamics of virus-host interactions.
Keywords: human respiratory syncytial virus; co-infections; spatial statistics
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Simeonov, I.; Gong, X.; Kim, O.; Poss, M.; Chiaromonte, F.; Fricks, J. Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections. Viruses 2010, 2, 2782-2802.
Simeonov I, Gong X, Kim O, Poss M, Chiaromonte F, Fricks J. Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections. Viruses. 2010; 2(12):2782-2802.
Simeonov, Ivan; Gong, Xiaoyan; Kim, Oekyung; Poss, Mary; Chiaromonte, Francesca; Fricks, John. 2010. "Exploratory Spatial Analysis of in vitro Respiratory Syncytial Virus Co-infections." Viruses 2, no. 12: 2782-2802.