Limits...
High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance.

Seng LG, Daly J, Chang KC, Kuchipudi SV - PLoS ONE (2014)

Bottom Line: We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells.IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs).Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.

ABSTRACT
Respiratory epithelial cells play a key role in influenza A virus (IAV) pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77) IAVs in normal primary human bronchial epithelial (NHBE) and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs). Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.

Show MeSH

Related in: MedlinePlus

BEAS-2B cells were more resistant than human primary NHBE cells and human A549 cells to human H1N1 (A) and avian H2N3 (B) influenza virus.Cells were infected with the respective virus at a dose that was equivalent to 1.0 MOI in MDCK cells. For both viruses, few BEAS-2B cells (a), most NHBE cells (b), and virtually all A549 cells (c) were positive for viral NP at 6 h of infection. At 24 h of infection with human H1N1 virus (C and D), M gene expression (C) and infectious virus production (D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells, with A549 cells showing the highest M gene expression (C) and infectious virus production (D). **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4196766&req=5

pone-0109023-g003: BEAS-2B cells were more resistant than human primary NHBE cells and human A549 cells to human H1N1 (A) and avian H2N3 (B) influenza virus.Cells were infected with the respective virus at a dose that was equivalent to 1.0 MOI in MDCK cells. For both viruses, few BEAS-2B cells (a), most NHBE cells (b), and virtually all A549 cells (c) were positive for viral NP at 6 h of infection. At 24 h of infection with human H1N1 virus (C and D), M gene expression (C) and infectious virus production (D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells, with A549 cells showing the highest M gene expression (C) and infectious virus production (D). **p<0.01.

Mentions: To compare the susceptibility of BEAS-2B cells with primary NHBE and A549 cells, the three cell types were infected with USSR H1N1 or avian H2N3 viruses at MOI of 1.0 (based on MDCK cells). Viral NP at 6 h of infection with H1N1 virus (Figure 3A) and H2N3 virus (Figure 3B) showed that few BEAS-2B cells, most NHBE cells and virtually all A549 cells were positive for viral NP. We then quantified viral M gene RNA expression and progeny virus release in all three cell type at 10 and 24 h of H1N1 virus infection. M gene expression (Figure 3C) and infectious virus production (Figure 3D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells at 24 h of H1N1 virus infection (p<0.05), with A549 cells showing the highest M gene expression (Figure 3C) and infectious virus production (Figure 3D).


High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance.

Seng LG, Daly J, Chang KC, Kuchipudi SV - PLoS ONE (2014)

BEAS-2B cells were more resistant than human primary NHBE cells and human A549 cells to human H1N1 (A) and avian H2N3 (B) influenza virus.Cells were infected with the respective virus at a dose that was equivalent to 1.0 MOI in MDCK cells. For both viruses, few BEAS-2B cells (a), most NHBE cells (b), and virtually all A549 cells (c) were positive for viral NP at 6 h of infection. At 24 h of infection with human H1N1 virus (C and D), M gene expression (C) and infectious virus production (D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells, with A549 cells showing the highest M gene expression (C) and infectious virus production (D). **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196766&req=5

pone-0109023-g003: BEAS-2B cells were more resistant than human primary NHBE cells and human A549 cells to human H1N1 (A) and avian H2N3 (B) influenza virus.Cells were infected with the respective virus at a dose that was equivalent to 1.0 MOI in MDCK cells. For both viruses, few BEAS-2B cells (a), most NHBE cells (b), and virtually all A549 cells (c) were positive for viral NP at 6 h of infection. At 24 h of infection with human H1N1 virus (C and D), M gene expression (C) and infectious virus production (D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells, with A549 cells showing the highest M gene expression (C) and infectious virus production (D). **p<0.01.
Mentions: To compare the susceptibility of BEAS-2B cells with primary NHBE and A549 cells, the three cell types were infected with USSR H1N1 or avian H2N3 viruses at MOI of 1.0 (based on MDCK cells). Viral NP at 6 h of infection with H1N1 virus (Figure 3A) and H2N3 virus (Figure 3B) showed that few BEAS-2B cells, most NHBE cells and virtually all A549 cells were positive for viral NP. We then quantified viral M gene RNA expression and progeny virus release in all three cell type at 10 and 24 h of H1N1 virus infection. M gene expression (Figure 3C) and infectious virus production (Figure 3D) from BEAS-2B cells were significantly less than corresponding NHBE and A549 cells at 24 h of H1N1 virus infection (p<0.05), with A549 cells showing the highest M gene expression (Figure 3C) and infectious virus production (Figure 3D).

Bottom Line: We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells.IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs).Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.

ABSTRACT
Respiratory epithelial cells play a key role in influenza A virus (IAV) pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77) IAVs in normal primary human bronchial epithelial (NHBE) and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs). Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.

Show MeSH
Related in: MedlinePlus