Enforced expression of microRNA-21 influences the replication of varicella-zoster virus by triggering signal transducer and activator of transcription 3.

Zhongrong Liu,Rina Wu,Jianyong Fan,Yan Li,Huilan Yang

doi:10.3892/etm.2014.1588

Abstract

Varicella-zoster virus (VZV) causes chronic pain and serious complications, including zoster paresis. However, the mechanism of VZV replication, a critical part of VZV pathogenesis, remains largely unknown and was investigated in the present study. The upregulation of microRNA-21 (miR-21) was identified following VZV infection in vitro by quantitative polymerase chain reaction. The hypothesis that the overexpression of miR-21 activates the signal transducer and activator of transcription 3 (STAT3) signaling pathway was validated by measuring the mRNA expression levels of STAT3 and the anti-apoptotic protein survivin in human malignant melanoma (MeWo) and human embryonic lung fibroblast (HELF) cell lines transfected with miR-21-mimic and comparing them with those in cells transfected with miR-control. To further study the interaction of miR-21, STAT3 and VZV replication, the effects of miR-21 overexpression and STAT3 knockdown were evaluated. Higher virus titers were detected when miR-21 was upregulated in vitro. Moreover, it was identified that significantly lower virus titers were present in MeWo cells in which STAT3 was knocked down. In addition, the overexpression of miR-21 did not stimulate VZV replication in the MeWo cell line when the STAT3 gene was silenced. Therefore, the observations of the present study indicate that the enforced expression of miR-21 promotes the replication of VZV by activating STAT3 in vitro.

Highlights

Varicella‐zoster virus (VZV) belongs to the α‐herpesvirus family and causes varicella with primary infection and zoster during reactivation from a latent state
Results miR‐21 expression increases in human embryonic lung fibroblast (HELF) and MeWo cell lines following VZV infection. miR‐21 has a multifunctional role in virus infection
To demonstrate the effect that miR‐21 has on VZV infection, the expression of miR‐21 in HELF and MeWo was examined by relative quantitative polymerase chain reaction (qPCR) following VZV infection

Summary

Introduction

Varicella‐zoster virus (VZV) belongs to the α‐herpesvirus family and causes varicella (chickenpox) with primary infection and zoster (shingles) during reactivation from a latent state. The life cycle of VZV relies on its tropism for T cells, skin and neurons [3,4,5]. VZV replication is an important part of the life cycle; the replication mechanisms remain largely unknown. It has been shown that miRNAs function to activate interferon (IFN)‐mediated antiviral activity, suppress the viral counter‐responses to cell restriction and affect the viral replication and the pathogenesis of viral infections [7]. MiRNAs have been documented to have diverse effects in terms of viral replication. Numerous other miRNAs function as inhibiting factors and interfere with viral replication. MiR‐501 increases HBV production via the same mechanism by which miR‐126 affects coxsackievirus [12,13]. MiRNAs may affect viral replication as suppressors or promoters. To date no miRNAs that impact the replication of VZV have been identified

Methods

Results

Conclusion