Role of host reticulon proteins in rearranging membranes for positive-strand RNA virus replication

Abstract

Positive-strand RNA [(+)RNA] viruses are responsible for numerous human, animal, and plant diseases. Because of the limiting coding capacity of (+)RNA viruses, their replication requires a complex orchestration of interactions between the viral genome, viral proteins and exploited host factors. To replicate their genomic RNAs, (+)RNA viruses induce membrane rearrangements that create membrane-linked RNA replication compartments. Along with substantial advances on the ultrastructure of the membrane-bound RNA replication compartments, recent results have shed light into the role that host factors play in rearranging these membranes. This review focuses on recent insights that have driven a new understanding of the role that the membrane-shaping host reticulon homology domain proteins (RHPs) play in facilitating the replication of various (+)RNA viruses.

Figure 1

Positive and negative curvature found within viral induced replication compartments. (a) RHPs (red) induce curvature by protruding the membrane towards the cytoplasm to form tubules. (b) BMV replicase protein 1a (blue) forms spherules by invaginating the membrane away from the cytoplasm. (c) In viral induced vesicles that remain connected to the parental membrane, the area around the neck has positive curvature while the body of the vesicle has negative curvature. (d) Model for potential role of RHPs in formation and/or maintenance of BMV induced spherules. 1a (blue arc) might induce and stabilize negative curvature in the vesicle body whereas RHPs (red arcs) would partially cancel negative curvature at the body to allow expansion of the vesicle and stabilize the spherule neck. The poliovirus membranous replication complexes found in early (e) and late (f) stages of development both have positive curvature. For (f), cyan and orange indicate inner and outer membrane of double-membrane structures.