Abstract
Plant positive strand RNA viruses are intracellular infectious agents that take advantage of cellular lipids and membranes to support replication and protect viral RNA from degradation by host antiviral responses. In this review, we discuss how Tomato bushy stunt virus (TBSV) co-opts lipid transfer proteins and modulates lipid metabolism and transport to facilitate the assembly of the membrane-bound viral replicase complexes within intricate replication compartments. Identification and characterization of the proviral roles of specific lipids and proteins involved in lipid metabolism based on results from yeast (Saccharomyces cerevisiae) model host and cell-free approaches are discussed. The review also highlights the advantage of using liposomes with chemically defined composition to identify specific lipids required for TBSV replication. Remarkably, all the known steps in TBSV replication are dependent on cellular lipids and co-opted membranes.
Highlights
An intriguing aspect of (+)RNA virus replication is the close association of viral replicase complexes (VRCs) with subcellular membranes in plant or animal cells
Subsequent detailed analysis of the roles of various phospholipids in p92pol activation has revealed the stimulatory function of PE and PC on the in vitro RNA-dependent RNA polymerase (RdRp) activity, while PG showed a dominant inhibitory effect on RdRp activation and binding of p92pol to the viral (+)RNA [54]. These results suggest that the phospholipid composition around the Tomato bushy stunt virus (TBSV) p92pol affects RdRp activity
Third process is the VRC assembly, which is driven by interactions between p33 replication protein, membrane-bending proteins, such as the co-opted cellular endosomal sorting complex required for transport (ESCRT) proteins, and mostly PE and other phospholipids and sterols in subcellular membranes
Summary
An intriguing aspect of (+)RNA virus replication is the close association of viral replicase complexes (VRCs) with subcellular membranes in plant or animal cells. The membranous structures help the virus evade cellular defense mechanisms and protect the viral RNA from degradation. This is facilitated by virus-orchestrated membrane deformations leading to generation of spherules, which are vesicle-like membrane invaginations with narrow openings towards the cytosol, or single- and double-membrane vesicles that harbor VRCs [1,2]. Among the hottest topics in plant virology include approaches to gain deeper insights into the interaction of viral replication proteins with subcellular membranes and lipids and the virus-driven modification of lipid metabolism and transport.
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