Open Access

Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation

  • Authors:
    • Qiuqin Feng
    • Zhonglan Su
    • Shiyu Song
    • Hui Χu
    • Bin Zhang
    • Long Yi
    • Man Tian
    • Hongwei Wang
  • View Affiliations

  • Published online on: July 26, 2016     https://doi.org/10.3892/ijmm.2016.2691
  • Pages: 812-822
  • Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS‑2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro‑inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of RSV infection validated these results. Treatment with HDACis alleviated airway inflammation and reduced in vivo RSV replication. Our data demonstrated that RSV reduced histone acetylation by enhancing HDAC2 expression. Treatment with HDACis (TSA/SAHA) significantly inhibited RSV replication and decreased RSV-induced airway inflammation and oxidative stress. Therefore, the inhibition of HDACs represents a novel therapeutic approach in modulating RSV-induced lung disease.
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September-2016
Volume 38 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Feng Q, Su Z, Song S, Χu H, Zhang B, Yi L, Tian M and Wang H: Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation. Int J Mol Med 38: 812-822, 2016
APA
Feng, Q., Su, Z., Song, S., Χu, H., Zhang, B., Yi, L. ... Wang, H. (2016). Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation. International Journal of Molecular Medicine, 38, 812-822. https://doi.org/10.3892/ijmm.2016.2691
MLA
Feng, Q., Su, Z., Song, S., Χu, H., Zhang, B., Yi, L., Tian, M., Wang, H."Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation". International Journal of Molecular Medicine 38.3 (2016): 812-822.
Chicago
Feng, Q., Su, Z., Song, S., Χu, H., Zhang, B., Yi, L., Tian, M., Wang, H."Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation". International Journal of Molecular Medicine 38, no. 3 (2016): 812-822. https://doi.org/10.3892/ijmm.2016.2691