Viral sensing of the subcellular environment regulates 3 the assembly of new viral replicase complexes during 4 the course of infection

Replication of (+)RNA viruses depends on the availability of co-opted host 16 proteins and lipids. But how could viruses sense the accessibility of cellular resources? An 17 emerging concept based on tombusviruses, small plant viruses, is that viruses might 18 regulate viral replication at several steps depending on what cellular factors are available 19 at a given time point. The authors discuss the role of phospholipids, sterols and cellular 20 WW-domain proteins and eEF1A in control of activation of the viral RdRp and regulation 21 of the assembly of viral replicase complexes (VRC). These regulatory mechanisms might 22 explain how tombusviruses could adjust the efficiency of RNA replication and new VRC 23 assembly to the limiting resources of the host cells during infections. 24 25 Plus-stranded (+)RNA viruses, which are widespread pathogens of plants and animals, replicate in 26 the cytosol of infected cells. These viruses assemble membrane-bound viral replicase complexes 27 (VRCs), which consist of the viral RNA and viral proteins as well as co-opted host proteins (1-3). 28 After translation of the incoming viral (+)RNA in the cytosol, the VRC assembly takes place, 29 followed by robust RNA synthesis driven by the viral RNA-dependent RNA polymerase (RdRp) 30 located in the VRCs. After multiple cycles of translation/replication of the newly made (+)RNAs, 31 the viral (+)RNA progeny become encapsidated and a few (+)RNAs move to neighboring cells to 32 initiate new infections. The replication process is “expensive” for the cell because the virus steals 33 away numerous pro-viral host proteins, subverts lipids and subcellular membranes, and uses up 34 large amounts of amino acids, ATP and other ribonucleotides for VRC assembly and RNA 35 synthesis. The hijacked host proteins include translation factors, protein chaperones, RNA36 modifying enzymes, ESCRT proteins and cellular proteins involved in lipid biosynthesis (4, 5). 37 The emerging picture is that VRC assembly is driven by many factors, thus the assembly process 38 on July 3, 2017 by gest http/jvi.asm .rg/ D ow nladed fom