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Type I Interferon Response Is Delayed in Human Astrovirus Infections
Authors:Susana Guix  Anna Pérez-Bosque  Llu?sa Miró  Miquel Moretó  Albert Bosch  Rosa M Pintó
Institution:1. Enteric Virus Group, Department of Microbiology, University of Barcelona, Barcelona, Spain.; 2. Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Santa Coloma de Gramanet, Spain.; 3. Digestive Physiology and Nutritional Adaptations Group, Department of Physiology, University of Barcelona, Barcelona, Spain.; University of Tennessee Health Science Center, UNITED STATES,
Abstract:Type I interferon (IFN) activation and its subsequent effects are important in the response to viral infections. Here we show that human astroviruses (HAstVs), which are important agents of acute gastroenteritis in children, induce a mild and delayed IFN response upon infecting CaCo-2 cells. Although IFN-β mRNA is detected within infected cells and supernatant from infected cells show antiviral activity against the replication of other well-known IFN-sensitive viruses, these responses occur at late stages of infection once genome replication has taken place. On the other hand, HAstV replication can be partially reduced by the addition of exogenous IFN, and inhibition of IFN activation by BX795 enhances viral replication, indicating that HAstVs are IFN-sensitive viruses. Finally, different levels of IFN response were observed in cells infected with different HAstV mutants with changes in the hypervariable region of nsP1a/4, suggesting that nsP1a/4 genotype may potentially have clinical implications due to its correlation with the viral replication phenotype and the antiviral responses induced within infected cells.
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