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Retinoic acid receptor β, a potential therapeutic target in the inhibition of adenovirus replication.

Abstract：

:Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus-host interactions, and several key host molecules involved in the HAdV infection process were identified. The RARβ (retinoic acid receptor β) molecule, one of the upstream regulatory factors of differentially expressed genes (DEGs), played important roles in HAdV replication. The results of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that RARβ mRNA and protein were downregulated by HAdV infection in the A549 cells. The knockdown of RARβ by RARβ siRNA increased the HAdV production and the overexpression of RARβ decreased the HAdV production. Furthermore, FDA-approved Tazarotene, which is an RAR selective agonist with relatively more selectivity for RARβ, was found to inhibit HAdV replication in vitro. Taken together, our study presents a key host molecule in adenovirus infection, which could be developed as a potential host target to an anti-adenovirus drug. In addition, this study provides evidence for the re-exploitation of an FDA-approved small molecule for therapeutic applications in adenovirus replication.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Wang X,Zhang Q,Zhou Z,Liu M,Chen Y,Li J,Xu L,Guo J,Li Q,Yang J,Wang S

doi

10.1016/j.antiviral.2018.01.014

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

84-93

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(17)30711-8

journal_volume

152

pub_type

杂志文章

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