G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets

Pseudorabies virus (PRV) is the causative agent of Aujeszky’s disease, which still causes large economic losses for the swine industry. Therefore, it is urgent to find a new strategy to prevent and control PRV infection. Previous studies have proven that guanine (G)-rich DNA or RNA sequences in some...

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Autores principales:	Yance Zhu, Wenhao Liu, Chao Zhang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pseudorabies virus G-quadruplex DNA replication antiviral activity PhenDC3 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f7b351f23a4b4f229a067c4d01ef9c9e
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spelling	oai:doaj.org-article:f7b351f23a4b4f229a067c4d01ef9c9e2021-11-25T19:13:27ZG-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets10.3390/v131122191999-4915https://doaj.org/article/f7b351f23a4b4f229a067c4d01ef9c9e2021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2219https://doaj.org/toc/1999-4915Pseudorabies virus (PRV) is the causative agent of Aujeszky’s disease, which still causes large economic losses for the swine industry. Therefore, it is urgent to find a new strategy to prevent and control PRV infection. Previous studies have proven that guanine (G)-rich DNA or RNA sequences in some other viruses’ genomes have the potential to form G-quadruplex (G4), which serve as promising antivirus targets. In this study, we identified two novel G4-forming sequences, OriL-A and OriL-S, which are located at the upstream origin of replication (OriL) in the PRV genome and conserved across 32 PRV strains. Circular dichroism (CD) spectroscopy and a gel electrophoresis assay showed that the two G-rich sequences can fold into parallel G4 structures in vitro. Moreover, fluorescence resonance energy transfer (FRET) melting and a Taq polymerase stop assay indicated that the G4 ligand PhenDC3 has the capacity to bind and stabilize the G4. Notably, the treatment of PRV-infected cells with G4-stabilizer PhenDC3 significantly inhibited PRV DNA replication in host cells but did not affect PRV’s attachment and entry. These results not only expand our knowledge about the G4 characteristics in the PRV genome but also suggest that G4 may serve as an innovative therapeutic target against PRV.Yance ZhuWenhao LiuChao ZhangMDPI AGarticlepseudorabies virusG-quadruplexDNA replicationantiviral activityPhenDC3MicrobiologyQR1-502ENViruses, Vol 13, Iss 2219, p 2219 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pseudorabies virus G-quadruplex DNA replication antiviral activity PhenDC3 Microbiology QR1-502
spellingShingle	pseudorabies virus G-quadruplex DNA replication antiviral activity PhenDC3 Microbiology QR1-502 Yance Zhu Wenhao Liu Chao Zhang G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
description	Pseudorabies virus (PRV) is the causative agent of Aujeszky’s disease, which still causes large economic losses for the swine industry. Therefore, it is urgent to find a new strategy to prevent and control PRV infection. Previous studies have proven that guanine (G)-rich DNA or RNA sequences in some other viruses’ genomes have the potential to form G-quadruplex (G4), which serve as promising antivirus targets. In this study, we identified two novel G4-forming sequences, OriL-A and OriL-S, which are located at the upstream origin of replication (OriL) in the PRV genome and conserved across 32 PRV strains. Circular dichroism (CD) spectroscopy and a gel electrophoresis assay showed that the two G-rich sequences can fold into parallel G4 structures in vitro. Moreover, fluorescence resonance energy transfer (FRET) melting and a Taq polymerase stop assay indicated that the G4 ligand PhenDC3 has the capacity to bind and stabilize the G4. Notably, the treatment of PRV-infected cells with G4-stabilizer PhenDC3 significantly inhibited PRV DNA replication in host cells but did not affect PRV’s attachment and entry. These results not only expand our knowledge about the G4 characteristics in the PRV genome but also suggest that G4 may serve as an innovative therapeutic target against PRV.
format	article
author	Yance Zhu Wenhao Liu Chao Zhang
author_facet	Yance Zhu Wenhao Liu Chao Zhang
author_sort	Yance Zhu
title	G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
title_short	G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
title_full	G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
title_fullStr	G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
title_full_unstemmed	G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets
title_sort	g-quadruplexes formation at the upstream region of replication origin (oril) of the pseudorabies virus: implications for antiviral targets
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f7b351f23a4b4f229a067c4d01ef9c9e
work_keys_str_mv	AT yancezhu gquadruplexesformationattheupstreamregionofreplicationoriginorilofthepseudorabiesvirusimplicationsforantiviraltargets AT wenhaoliu gquadruplexesformationattheupstreamregionofreplicationoriginorilofthepseudorabiesvirusimplicationsforantiviraltargets AT chaozhang gquadruplexesformationattheupstreamregionofreplicationoriginorilofthepseudorabiesvirusimplicationsforantiviraltargets
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G-Quadruplexes Formation at the Upstream Region of Replication Origin (OriL) of the Pseudorabies Virus: Implications for Antiviral Targets

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