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Viruses 2015, 7(4), 1823-1831; doi:10.3390/v7041823

Analysis of HDAC6 and BAG3-Aggresome Pathways in African Swine Fever Viral Factory Formation

1
Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 10029 NY, USA
3
Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, 10029 NY, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Eric O. Freed
Received: 24 February 2015 / Revised: 27 March 2015 / Accepted: 1 April 2015 / Published: 8 April 2015
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [1128 KB, uploaded 12 May 2015]   |  

Abstract

African swine fever virus (ASFV) is a double-stranded DNA virus causing a hemorrhagic fever disease with high mortality rates and severe economic losses in pigs worldwide. ASFV replicates in perinuclear sites called viral factories (VFs) that are morphologically similar to cellular aggresomes. This fact raises the possibility that both VFs and aggresomes may be the same structure. However, little is known about the process involved in the formation of these viral replication platforms. In order to expand our knowledge on the assembly of ASFV replication sites, we have analyzed the involvement of both canonical aggresome pathways in the formation of ASFV VFs: HDAC6 and BAG3. HDAC6 interacts with a component of the dynein motor complex (dynactin/p150Glued) and ubiquitinated proteins, transporting them to the microtubule-organizing center (MTOC) and leading to aggresome formation, while BAG3 is mediating the recruitment of non-ubiquitinated proteins through a similar mechanism. Tubacin-mediated HDAC6 inhibition and silencing of BAG3 pathways, individually or simultaneously, did not prevent ASFV VF formation. These findings show that HDAC6 and Bag3 are not required for VFs formation suggesting that aggresomes and VFs are not the same structures. However, alternative unexplored pathways may be involved in the formation of aggresomes. View Full-Text
Keywords: African swine fever virus; aggresome; HDAC6; BAG3; viral factories African swine fever virus; aggresome; HDAC6; BAG3; viral factories
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Muñoz-Moreno, R.; Barrado-Gil, L.; Galindo, I.; Alonso, C. Analysis of HDAC6 and BAG3-Aggresome Pathways in African Swine Fever Viral Factory Formation. Viruses 2015, 7, 1823-1831.

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