Article

Intestinal epithelia activate anti-viral signaling via intracellular sensing of rotavirus structural components

Department of Pathology, Emory University, Atlanta, Georgia, USA.
Mucosal Immunology (Impact Factor: 7.37). 11/2010; 3(6):622-32. DOI: 10.1038/mi.2010.39
Source: PubMed

ABSTRACT

Rotavirus (RV), a leading cause of severe diarrhea, primarily infects intestinal epithelial cells (IECs) causing self-limiting illness. To better understand innate immunity to RV, we sought to define the extent to which IEC activation of anti-viral responses required viral replication or could be recapitulated by inactivated RV or its components. Using model human intestinal epithelia, we observed that RV-induced activation of signaling events and gene expression typically associated with viral infection was largely mimicked by administration of ultraviolet (UV)-inactivated RV. Use of anti-interferon (IFN) neutralizing antibodies revealed that such replication-independent anti-viral gene expression required type I IFN signaling. In contrast, RV-induction of nuclear factor-κB-mediated interleukin-8 expression was dependent on viral replication. The anti-viral gene expression induced by UV-RV was not significantly recapitulated by RV RNA or RV virus-like particles although the latter could enter IEC. Together, these results suggest that RV proteins mediate viral entry into epithelial cells leading to intracellular detection of RV RNA that generates an anti-viral response.

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    • "These molecules are typical of many viral infections including rotavirus. Viral dsRNA activate PRRs such as TLR3, RIG-I, and MDA-5, which signal host cellular responses in order to try to control viral infection [25-27]. IFNs and IFN-regulated gene products are then synthesized and play a key role in the host response for clearing viruses. "
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    Full-text · Article · May 2014 · BMC Microbiology
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    • "Other mechanisms of NF-kB activation have been proposed, such as the interaction of cytoplasmic rotavirus VP4 protein with cellular TRAF-binding proteins (LaMonica et al., 2001), and the action of NSP1 (Bagchi et al., 2010). UV-inactivated rotavirus can activate NF-kB and induce IL-8 expression, although with much less efficiency than replicating rotavirus, demonstrating that replication is required for efficient NF-kB-driven cytokine expression in intestinal cells (Casola et al., 1998; Frias et al., 2010; Holloway & Coulson, 2006; Rollo et al., 1999). "
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    ABSTRACT: Rotavirus is a leading cause of severe dehydrating diarrhoea in infants and young children. Following rotavirus infection in the intestine an innate immune response is rapidly triggered. This response leads to the induction of type I and type III interferons (IFNs) and other cytokines, resulting in a reduction in viral replication. Here we review the current literature describing the detection of rotavirus infection by pattern recognition receptors within host cells, the subsequent molecular mechanisms leading to IFN and cytokine production, and the processes leading to reduced rotavirus replication and the development of protective immunity. Rotavirus countermeasures against innate responses, and their roles in modulating rotavirus replication in mice, also are discussed. By linking these different aspects of innate immunity we provide a comprehensive overview of the host's first line of defence against rotavirus infection. Understanding these processes is expected to be of benefit in improving strategies to combat rotavirus disease.
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