African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle

Abstract African swine fever virus is the etiological agent of a contagious and fatal acute haemorrhagic viral disease for which there are no vaccines or therapeutic options. The ASFV encodes for a putative E2 ubiquitin conjugating enzyme (ORF I215L) that shows sequence homology with eukaryotic coun...

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Autores principales:	Ferdinando B. Freitas, Gonçalo Frouco, Carlos Martins, Fernando Ferreira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b6c061dd51143fd9bedc5a674e60d3c
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spelling	oai:doaj.org-article:7b6c061dd51143fd9bedc5a674e60d3c2021-12-02T12:32:10ZAfrican swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle10.1038/s41598-018-21872-22045-2322https://doaj.org/article/7b6c061dd51143fd9bedc5a674e60d3c2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21872-2https://doaj.org/toc/2045-2322Abstract African swine fever virus is the etiological agent of a contagious and fatal acute haemorrhagic viral disease for which there are no vaccines or therapeutic options. The ASFV encodes for a putative E2 ubiquitin conjugating enzyme (ORF I215L) that shows sequence homology with eukaryotic counterparts. In the present study, we showed that pI215L acts as an E2-ubiquitin like enzyme in a large range of pH values and temperatures, after short incubation times. Further experiments revealed that pI215L is polyubiquitinated instead of multi-mono-ubiquitinated and Cys85 residue plays an essential role in the transthioesterification reaction. In infected cells, I215L gene is transcribed from 2 hours post infection and immunoblot analysis confirmed that pI215L is expressed from 4 hpi. Immunofluorescence studies revealed that pI215L is recruited to viral factories from 8 hpi and a diffuse distribution pattern throughout the nucleus and cytoplasm. siRNA studies suggested that pI215L plays a critical role in the transcription of late viral genes and viral DNA replication. Altogether, our results emphasize the potential use of this enzyme as target for drug and vaccine development against ASF.Ferdinando B. FreitasGonçalo FroucoCarlos MartinsFernando FerreiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ferdinando B. Freitas Gonçalo Frouco Carlos Martins Fernando Ferreira African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
description	Abstract African swine fever virus is the etiological agent of a contagious and fatal acute haemorrhagic viral disease for which there are no vaccines or therapeutic options. The ASFV encodes for a putative E2 ubiquitin conjugating enzyme (ORF I215L) that shows sequence homology with eukaryotic counterparts. In the present study, we showed that pI215L acts as an E2-ubiquitin like enzyme in a large range of pH values and temperatures, after short incubation times. Further experiments revealed that pI215L is polyubiquitinated instead of multi-mono-ubiquitinated and Cys85 residue plays an essential role in the transthioesterification reaction. In infected cells, I215L gene is transcribed from 2 hours post infection and immunoblot analysis confirmed that pI215L is expressed from 4 hpi. Immunofluorescence studies revealed that pI215L is recruited to viral factories from 8 hpi and a diffuse distribution pattern throughout the nucleus and cytoplasm. siRNA studies suggested that pI215L plays a critical role in the transcription of late viral genes and viral DNA replication. Altogether, our results emphasize the potential use of this enzyme as target for drug and vaccine development against ASF.
format	article
author	Ferdinando B. Freitas Gonçalo Frouco Carlos Martins Fernando Ferreira
author_facet	Ferdinando B. Freitas Gonçalo Frouco Carlos Martins Fernando Ferreira
author_sort	Ferdinando B. Freitas
title	African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
title_short	African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
title_full	African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
title_fullStr	African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
title_full_unstemmed	African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
title_sort	african swine fever virus encodes for an e2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/7b6c061dd51143fd9bedc5a674e60d3c
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African swine fever virus encodes for an E2-ubiquitin conjugating enzyme that is mono- and di-ubiquitinated and required for viral replication cycle

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