Abstract
Replication of plus-stranded RNA [(+)RNA] viruses depends on the availability of coopted host proteins and lipids. But, how could viruses sense the accessibility of cellular resources? An emerging concept based on tombusviruses, small plant viruses, is that viruses might regulate viral replication at several steps depending on what cellular factors are available at a given time point. I discuss the role of phospholipids, sterols, and cellular WW domain proteins and eukaryotic elongation factor 1A (eEF1A) in control of activation of the viral RNA-dependent RNA polymerase (RdRp) and regulation of the assembly of viral replicase complexes (VRCs). These regulatory mechanisms might explain how tombusviruses could adjust the efficiency of RNA replication and new VRC assembly to the limiting resources of the host cells during infections.
Document Type
Article
Publication Date
5-2015
Digital Object Identifier (DOI)
http://dx.doi.org/10.1128/JVI.02973-14
Funding Information
This research was supported by the NIH-NIAID (1R21AI109529).
Repository Citation
Nagy, Peter D., "Viral Sensing of the Subcellular Environment Regulates the Assembly of New Viral Replicase Complexes During the Course of Infection" (2015). Plant Pathology Faculty Publications. 41.
https://uknowledge.uky.edu/plantpath_facpub/41
Figure 1 JPEG: Coopted host factors and regulation of tombusvirus replication. At the early stage of replication, the tombusvirus p33 and p92 replication proteins bind primarily to the abundant cellular susceptibility factors (proviral host factors, in blue), to other viral replication proteins, and the viral (+)RNA to recruit the viral (+)RNA to PE- and sterol-rich cellular membranes (located at or near membrane contact sites) to assemble functional VRCs. At the late stage of replication, the host factors have been depleted due to sequestration into previously assembled VRCs, and the new viral replication proteins bind to WW domain proteins, blocking new VRC assembly (regulation 1). A shortage in Efm4-methylated eEF1A leads to degradation of p33 and p92 RdRp (regulation 2). Alternatively, limitation in PE-rich (regulation 3) and sterol-rich (regulation 4) membranes or p92 RdRp binding to PG leads to inactive RdRp, inhibiting new viral RNA synthesis at the late stage of replication. PC, phosphatidylcholine.
J. Virol. 2015 May 89(10) 5196-9, FIG 1.ppt (401 kB)
Figure 1 Powerpoint: Coopted host factors and regulation of tombusvirus replication. At the early stage of replication, the tombusvirus p33 and p92 replication proteins bind primarily to the abundant cellular susceptibility factors (proviral host factors, in blue), to other viral replication proteins, and the viral (+)RNA to recruit the viral (+)RNA to PE- and sterol-rich cellular membranes (located at or near membrane contact sites) to assemble functional VRCs. At the late stage of replication, the host factors have been depleted due to sequestration into previously assembled VRCs, and the new viral replication proteins bind to WW domain proteins, blocking new VRC assembly (regulation 1). A shortage in Efm4-methylated eEF1A leads to degradation of p33 and p92 RdRp (regulation 2). Alternatively, limitation in PE-rich (regulation 3) and sterol-rich (regulation 4) membranes or p92 RdRp binding to PG leads to inactive RdRp, inhibiting new viral RNA synthesis at the late stage of replication. PC, phosphatidylcholine.
Notes/Citation Information
Published in Journal of Virology, v. 89, no. 10, p. 5196-5199.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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