Dynamic lipid landscape of picornavirus replication organelles

Abstract

Picornavirus infection induces rapid reorganization of the cellular membrane architecture and appearance of novel membranous structures associated with the viral RNA replication and virion assembly-replication organelles. Recent studies significantly advanced our understanding of their lipid composition and cellular mechanisms involved in their development. Picornaviruses activate synthesis of both structural and signaling lipids and reroute cellular cholesterol trafficking pathways to create unique membranous domains favoring viral replication. Rapidly replicating picornaviruses rely on posttranslational activation and/or specific recruitment of cellular proteins rather than on modulation of expression of cellular genes to create favorable membrane microenvironment. At the same time picornaviruses demonstrate remarkable adaptability to changes in the lipid landscape which should be taken into account when developing novel antiviral strategies.

Figure 1. Picornavirus infection induces the development of unique membranous structures - replication organelles.

A. Scheme of poliovirus genome RNA indicating involvement of the viral proteins in rerouting of the cellular lipid synthesis and trafficking pathways resulting in expansion of membranes enriched in cholesterol and PI4P. B. An EM image of a poliovirus-infected HeLa cell at the end of infectious cycle (8 h post infection). The image is courtesy of Prof. Kurt Bienz, University of Zurich, Switzerland. C. Electron tomography reconstruction of poliovirus replication membranes at the middle of infectious cycle (4h post infection). Modified from [10].