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Type I interferon response is delayed in human astrovirus infections.

Guix S, Pérez-Bosque A, Miró L, Moretó M, Bosch A, Pintó RM - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Enteric Virus Group, Department of Microbiology, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Santa Coloma de Gramanet, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of nsP1a/4 genotype on the level of IFN-β response.Normalized levels of IFN-β/GAPDH response at 24 hpi were plotted against the average number of HAstV genome copies per infected cell after infecting differentiated CaCo-2 cells with different nsP1a/4 mutants at the same MOI. Data summarize results from three independent experiments.
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pone.0123087.g008: Effect of nsP1a/4 genotype on the level of IFN-β response.Normalized levels of IFN-β/GAPDH response at 24 hpi were plotted against the average number of HAstV genome copies per infected cell after infecting differentiated CaCo-2 cells with different nsP1a/4 mutants at the same MOI. Data summarize results from three independent experiments.

Mentions: Since viruses containing different nsP1a/4 variants have been associated with higher replication phenotypes and higher levels of virus shedding in stools, we evaluated whether nsP1a/4 variability influences the magnitude of the IFN-β response. CaCo-2 cells were infected at a MOI of 2 or 10 with different HAstV mutants differing in their nsP1a/4 HVR. IFN-β activation was measured by qRT-PCR and normalized versus GAPDH, and the average number of viral genome copies per infected cell was estimated after quantifying total HAstV RNA by qRT-PCR and normalizing it by the number of infected cells within each well. The average number of log HAstV genome copies per infected cell was, 5.8±0.9, 5.9±0.7, and 5.6 ± 0.6 for HAstV-IV, HAstV-VI and HAstV-XII, respectively. Results shown in Fig 8 indicate differences between HAstV mutants in terms of IFN-β activation. The level of IFN-β response in cells infected with HAstV containing nsP1a/4 genotype IV was lower than the IFN response induced by mutants HAstV-VI and XII, especially when the number of HAstV genomes per infected cell was high.


Type I interferon response is delayed in human astrovirus infections.

Guix S, Pérez-Bosque A, Miró L, Moretó M, Bosch A, Pintó RM - PLoS ONE (2015)

Effect of nsP1a/4 genotype on the level of IFN-β response.Normalized levels of IFN-β/GAPDH response at 24 hpi were plotted against the average number of HAstV genome copies per infected cell after infecting differentiated CaCo-2 cells with different nsP1a/4 mutants at the same MOI. Data summarize results from three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383485&req=5

pone.0123087.g008: Effect of nsP1a/4 genotype on the level of IFN-β response.Normalized levels of IFN-β/GAPDH response at 24 hpi were plotted against the average number of HAstV genome copies per infected cell after infecting differentiated CaCo-2 cells with different nsP1a/4 mutants at the same MOI. Data summarize results from three independent experiments.
Mentions: Since viruses containing different nsP1a/4 variants have been associated with higher replication phenotypes and higher levels of virus shedding in stools, we evaluated whether nsP1a/4 variability influences the magnitude of the IFN-β response. CaCo-2 cells were infected at a MOI of 2 or 10 with different HAstV mutants differing in their nsP1a/4 HVR. IFN-β activation was measured by qRT-PCR and normalized versus GAPDH, and the average number of viral genome copies per infected cell was estimated after quantifying total HAstV RNA by qRT-PCR and normalizing it by the number of infected cells within each well. The average number of log HAstV genome copies per infected cell was, 5.8±0.9, 5.9±0.7, and 5.6 ± 0.6 for HAstV-IV, HAstV-VI and HAstV-XII, respectively. Results shown in Fig 8 indicate differences between HAstV mutants in terms of IFN-β activation. The level of IFN-β response in cells infected with HAstV containing nsP1a/4 genotype IV was lower than the IFN response induced by mutants HAstV-VI and XII, especially when the number of HAstV genomes per infected cell was high.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Enteric Virus Group, Department of Microbiology, University of Barcelona, Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Santa Coloma de Gramanet, Spain.

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.

No MeSH data available.


Related in: MedlinePlus