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Viral Replication Protein Inhibits Cellular Cofilin Actin Depolymerization Factor to Regulate the Actin Network and Promote Viral Replicase Assembly
- Source :
- PLoS Pathogens, PLoS Pathogens, Vol 12, Iss 2, p e1005440 (2016)
- Publication Year :
- 2016
- Publisher :
- Public Library of Science, 2016.
-
Abstract
- RNA viruses exploit host cells by co-opting host factors and lipids and escaping host antiviral responses. Previous genome-wide screens with Tomato bushy stunt virus (TBSV) in the model host yeast have identified 18 cellular genes that are part of the actin network. In this paper, we show that the p33 viral replication factor interacts with the cellular cofilin (Cof1p), which is an actin depolymerization factor. Using temperature-sensitive (ts) Cof1p or actin (Act1p) mutants at a semi-permissive temperature, we find an increased level of TBSV RNA accumulation in yeast cells and elevated in vitro activity of the tombusvirus replicase. We show that the large p33 containing replication organelle-like structures are located in the close vicinity of actin patches in yeast cells or around actin cable hubs in infected plant cells. Therefore, the actin filaments could be involved in VRC assembly and the formation of large viral replication compartments containing many individual VRCs. Moreover, we show that the actin network affects the recruitment of viral and cellular components, including oxysterol binding proteins and VAP proteins to form membrane contact sites for efficient transfer of sterols to the sites of replication. Altogether, the emerging picture is that TBSV, via direct interaction between the p33 replication protein and Cof1p, controls cofilin activities to obstruct the dynamic actin network that leads to efficient subversion of cellular factors for pro-viral functions. In summary, the discovery that TBSV interacts with cellular cofilin and blocks the severing of existing filaments and the formation of new actin filaments in infected cells opens a new window to unravel the way by which viruses could subvert/co-opt cellular proteins and lipids. By regulating the functions of cofilin and the actin network, which are central nodes in cellular pathways, viruses could gain supremacy in subversion of cellular factors for pro-viral functions.<br />Author Summary The actin network, which is a central node in cellular pathways, is frequently targeted by various pathogens to modulate cellular responses. In this paper, the authors show that TBSV interacts with cofilin actin depolymerization factor leading to inhibition of the dynamic function of the actin network in infected cells. This allows TBSV to utilize the existing actin filaments to efficiently recruit host proteins and lipids for viral replication and to build viral replication compartments for robust viral replication. Altogether, subversion of the actin network by TBSV is a key step for the virus to gain access to cellular resources required for virus replication.
- Subjects :
- 0301 basic medicine
Leaves
Cell Membranes
Arp2/3 complex
Actin Filaments
Plant Science
Microfilament
Virus Replication
Biochemistry
Tombusvirus
Contractile Proteins
lcsh:QH301-705.5
biology
Plant Anatomy
Cofilin
Cell biology
Cell Motility
Profilin
Host-Pathogen Interactions
Dynamic Actin Filaments
RNA, Viral
Cellular Structures and Organelles
Cellular Types
Research Article
lcsh:Immunologic diseases. Allergy
DNA Replication
Plant Cell Biology
Immunology
macromolecular substances
Microbiology
03 medical and health sciences
Viral Proteins
Virology
Plant Cells
Genetics
Actin-binding protein
Molecular Biology
Virus Assembly
Organisms
Fungi
Actin remodeling
Biology and Life Sciences
Proteins
Membrane Proteins
Cell Biology
Yeast
Actins
Viral Replication
Cytoskeletal Proteins
030104 developmental biology
Destrin
lcsh:Biology (General)
Viral replication
biology.protein
Parasitology
MDia1
lcsh:RC581-607
Subjects
Details
- Language :
- English
- ISSN :
- 15537374 and 15537366
- Volume :
- 12
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens
- Accession number :
- edsair.doi.dedup.....7dd5fcdfc53659dfd847769d685b26bd