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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

Induction of an IFN response is delayed during HAstV infection.(A) Temporal analysis of induction of IFN-β and ISG56 mRNA expression by in CaCo-2 cells infected with HAstV at a MOI of 1. Mock-infected cells, cells treated for 24 h with exogenous IFN at 1,000 U/ml, and polyI:C-transfected cells were used as controls. (B) HAstV growth curve on CaCo-2 cells at 2 different MOIs. Total HAstV RNA was measured by qRT-PCR at the indicated times post-infection. Data represent mean values of duplicate wells and error bars represent the standard error of the mean (SEM).
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pone.0123087.g001: Induction of an IFN response is delayed during HAstV infection.(A) Temporal analysis of induction of IFN-β and ISG56 mRNA expression by in CaCo-2 cells infected with HAstV at a MOI of 1. Mock-infected cells, cells treated for 24 h with exogenous IFN at 1,000 U/ml, and polyI:C-transfected cells were used as controls. (B) HAstV growth curve on CaCo-2 cells at 2 different MOIs. Total HAstV RNA was measured by qRT-PCR at the indicated times post-infection. Data represent mean values of duplicate wells and error bars represent the standard error of the mean (SEM).

Mentions: To examine whether HAstV infection induces an IFN response, CaCo-2 cells were infected at a MOI of 1 and RNA was extracted at 0, 3, 12 and 24 hpi (Fig 1A). Mock-infected cells, cells transfected with polyI:C and cells treated with 1,000 U/ml of recombinant type I IFN were used as controls. Conventional RT-PCR was performed to detect viral RNA, IFN-β mRNA, and ISG56 mRNA. GAPDH mRNA was amplified as a quality control for RNA. Results show that polyI:C transfection induced IFN-β gene transcription as early as 3 hours post-transfection (hpt), while IFN-β mRNA could not be detected in HAstV-infected cells before 24 hpi. A time course analysis of HAstV RNA synthesis was performed by qRT-PCR after infecting cells at 2 different MOIs. As expected, a 3-log increase in viral RNA titers was observed during the first 24 hours for both MOIs (Fig 1B). Together, these results suggest that HAstV delays the onset of IFN induction sufficiently until a large amount of progeny particles are produced.


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)

Induction of an IFN response is delayed during HAstV infection.(A) Temporal analysis of induction of IFN-β and ISG56 mRNA expression by in CaCo-2 cells infected with HAstV at a MOI of 1. Mock-infected cells, cells treated for 24 h with exogenous IFN at 1,000 U/ml, and polyI:C-transfected cells were used as controls. (B) HAstV growth curve on CaCo-2 cells at 2 different MOIs. Total HAstV RNA was measured by qRT-PCR at the indicated times post-infection. Data represent mean values of duplicate wells and error bars represent the standard error of the mean (SEM).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0123087.g001: Induction of an IFN response is delayed during HAstV infection.(A) Temporal analysis of induction of IFN-β and ISG56 mRNA expression by in CaCo-2 cells infected with HAstV at a MOI of 1. Mock-infected cells, cells treated for 24 h with exogenous IFN at 1,000 U/ml, and polyI:C-transfected cells were used as controls. (B) HAstV growth curve on CaCo-2 cells at 2 different MOIs. Total HAstV RNA was measured by qRT-PCR at the indicated times post-infection. Data represent mean values of duplicate wells and error bars represent the standard error of the mean (SEM).
Mentions: To examine whether HAstV infection induces an IFN response, CaCo-2 cells were infected at a MOI of 1 and RNA was extracted at 0, 3, 12 and 24 hpi (Fig 1A). Mock-infected cells, cells transfected with polyI:C and cells treated with 1,000 U/ml of recombinant type I IFN were used as controls. Conventional RT-PCR was performed to detect viral RNA, IFN-β mRNA, and ISG56 mRNA. GAPDH mRNA was amplified as a quality control for RNA. Results show that polyI:C transfection induced IFN-β gene transcription as early as 3 hours post-transfection (hpt), while IFN-β mRNA could not be detected in HAstV-infected cells before 24 hpi. A time course analysis of HAstV RNA synthesis was performed by qRT-PCR after infecting cells at 2 different MOIs. As expected, a 3-log increase in viral RNA titers was observed during the first 24 hours for both MOIs (Fig 1B). Together, these results suggest that HAstV delays the onset of IFN induction sufficiently until a large amount of progeny particles are produced.

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