Gastrointestinal Influences on Poliovirus Replication, Dissemination and Pathogenesis in Mice

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Title: Gastrointestinal Influences on Poliovirus Replication, Dissemination and Pathogenesis in Mice
Author: Kuss, Sharon Kay
Abstract: Enteric viruses are transmitted between individuals by fecal -oral spread . After oral acquisition , enteric viruses encounter a complex environment within the gastrointestinal (GI ) tract , including pH changes , mucus , resident bacteria and a variety of epithelial and immune cell types . Little is known about how factors within and comprising the GI tract influence viral replication , dissemination and pathogenesis . In order to assess the influence of the intestinal environment on enteric viruses , poliovirus was used as a model enteric virus . Following infection within the GI tract , poliovirus has the capacity to spread to the central nervous system (CNS ) . Poliovirus infection of the CNS is uncommon , but it can result in acute flaccid paralysis known as poliomyelitis in humans . Poliomyelitis can be mimicked in mice susceptible to poliovirus . Initial studies were performed in mice to examine poliovirus infection within and dissemination from the GI tract to extra -intestinal tissues , including blood and the CNS . By monitoring spread of a marked poliovirus population in susceptible mice , many host barriers to intra -host viral trafficking were identified . Type I interferon responses and intestinal epithelial cell integrity are host barriers that were found to restrict poliovirus . Infecting cells within the GI tract was also difficult for poliovirus , which further limited dissemination from the intestine to the blood and CNS . Bottlenecks were imposed on poliovirus while trafficking through and disseminating from the GI tract , possibly providing an explanation for the low incidence of poliomyelitis disease onset in humans following poliovirus infection . Because the GI tract was a substantial barrier to poliovirus , studies were undertaken to characterize factors that limit poliovirus dissemination from the GI tract . The naturally -residing microbiota are amongst many other factors present within the GI tract that may influence poliovirus infection . Although suspected to limit poliovirus , intestinal microbiota augmented poliovirus infection in mice and cell culture by enhancing viral infectivity . The studies described herein demonstrate how host complexity imparts detrimental and beneficial influences on poliovirus acquired by the natural fecal -oral route .
URI: http : / /hdl .handle .net /2152 .5 /945
Date: 2011-12-12


Gastrointestinal Influences on Poliovirus Replication, Dissemination and Pathogenesis in Mice. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /945 .

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