title: Analysis of HDAC6 and BAG3-aggresome pathways in African swine fever viral factory formation.
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.
authors: Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain. raquel.munoz@mssm.edu.|Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, 10029 NY, USA. raquel.munoz@mssm.edu.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, 10029 NY, USA. raquel.munoz@mssm.edu.
authors: Raquel
authors: R
authors: Muñoz-Moreno
authors: Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain. barrado.lucia@inia.es.
authors: Lucía
authors: L
authors: Barrado-Gil
authors: Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain. galindo@inia.es.
authors: Inmaculada
authors: I
authors: Galindo
authors: Department of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28040 Madrid, Spain. calonso@inia.es.
authors: Covadonga
authors: C
authors: Alonso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000358:African Swine Fever Virus / Q000502:physiology*; D000818:Animals; D002460:Cell Line; D006655:Histone Deacetylases / Q000378:metabolism; D054884:Host-Pathogen Interactions; D013552:Swine; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D006655:Histone Deacetylases