Limits...
Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors.

Sasvari Z, Alatriste Gonzalez P, Nagy PD - Front Plant Sci (2014)

Bottom Line: The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae), which is developed as an advanced model organism.Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5'-3' exoribonuclease, Act1p actin protein and Cse4p centromere protein.These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Pathology, University of Kentucky Lexington, KY, USA.

ABSTRACT
To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF) are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae), which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5'-3' exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as "guardians" of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

No MeSH data available.


Related in: MedlinePlus

Physical and genetic protein interaction networks including XRN1, ACT1, and CSE4 CIRFs. See further details in the legend to Figure 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4127529&req=5

Figure 3: Physical and genetic protein interaction networks including XRN1, ACT1, and CSE4 CIRFs. See further details in the legend to Figure 2.

Mentions: The protein network map (Figure 2) with the previously identified cell-intrinsic TBSV restriction factors reveals several interesting observations. First, the yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5′–3′ exoribonuclease, and the not-yet characterized (as anti-TBSV proteins) Act1p actin protein and Cse4p centromere protein (Figure 2, marked with arrows and Figure 3). The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones (Figure 2, see also below), and the ribosomal or ribosome-associated factors, whose antiviral activities have not yet been characterized in further details. These possibly key host proteins [the so-called hub proteins with high connectivity in cellular protein-protein interaction network (Tsai et al., 2009)] might target important viral components or host factors to inhibit TBSV replication. Interestingly, the protein network map excludes 8 CIRFs (Table 1). These factors might work as single antiviral factors, or their interactions map is not yet complete, thus leading to their omission from our protein network map (Figure 2).


Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors.

Sasvari Z, Alatriste Gonzalez P, Nagy PD - Front Plant Sci (2014)

Physical and genetic protein interaction networks including XRN1, ACT1, and CSE4 CIRFs. See further details in the legend to Figure 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4127529&req=5

Figure 3: Physical and genetic protein interaction networks including XRN1, ACT1, and CSE4 CIRFs. See further details in the legend to Figure 2.
Mentions: The protein network map (Figure 2) with the previously identified cell-intrinsic TBSV restriction factors reveals several interesting observations. First, the yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5′–3′ exoribonuclease, and the not-yet characterized (as anti-TBSV proteins) Act1p actin protein and Cse4p centromere protein (Figure 2, marked with arrows and Figure 3). The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones (Figure 2, see also below), and the ribosomal or ribosome-associated factors, whose antiviral activities have not yet been characterized in further details. These possibly key host proteins [the so-called hub proteins with high connectivity in cellular protein-protein interaction network (Tsai et al., 2009)] might target important viral components or host factors to inhibit TBSV replication. Interestingly, the protein network map excludes 8 CIRFs (Table 1). These factors might work as single antiviral factors, or their interactions map is not yet complete, thus leading to their omission from our protein network map (Figure 2).

Bottom Line: The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae), which is developed as an advanced model organism.Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5'-3' exoribonuclease, Act1p actin protein and Cse4p centromere protein.These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase.

View Article: PubMed Central - PubMed

Affiliation: Department of Plant Pathology, University of Kentucky Lexington, KY, USA.

ABSTRACT
To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF) are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae), which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5'-3' exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as "guardians" of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

No MeSH data available.


Related in: MedlinePlus