Simvastatin modulates cellular components in influenza A virus-infected cells

Mehrbod,Parvaneh; Hair-Bejo,Mohd; Tengku Ibrahim,Tengku Azmi; Omar,Abdul Rahman; El Zowalaty,Mohamed; Ajdari,Zahra; Ideris,Aini

doi:10.3892/ijmm.2014.1761

Simvastatin modulates cellular components in influenza A virus-infected cells

Authors:
- Parvaneh Mehrbod
- Mohd Hair-Bejo
- Tengku Azmi Tengku Ibrahim
- Abdul Rahman Omar
- Mohamed El Zowalaty
- Zahra Ajdari
- Aini Ideris
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Affiliations: Institute of Bioscience, University Putra Malaysia, Serdang, Selangor 43400, Malaysia, School of Chemical Sciences and Food Technology, Faculty of Science and Technology, University Kebangsaan Malaysia, Bangi, Selangor 43600, Malaysia
Published online on: April 28, 2014 https://doi.org/10.3892/ijmm.2014.1761
Pages: 61-73
Copyright: © Mehrbod et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.

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