Membrane binding proteins of coronaviruses

J Alsaadi, Entedar A; Jones, Ian M

As noted above, the membranous vesicles or organelles of different morphologies induced by CoVs act as a platform for the formation of replication-transcription complexes (RTCs) and sequester newly formed RNAs away from host immune sensors [88, 89] . Both viral and hijacked host proteins are used in this process, taking advantage of cellular pathways and lipid modifying enzymes to the benefit of the virus [90, 91] . This usurping comes about through the future science group www.futuremedicine.com commandeering of normal secretory pathways used by noninfected cells to transport and deliver protein cargos; rather than encode proteins to build DMVs anew, CoVs redirect and reorganize the cellular processes already in place [92] . Two principle mechanisms have been described for moving and delivering cargo proteins through the secretory pathway; cisternal maturation and the formation of megavesicles [93] . In both cases the detail remains incomplete [94] . During CoV infection, such as for MHV, virions have been observed in large vesicle depots resembling megavesicles derived from Golgi/ERGIC membranes, indicating that remodeling of the Golgi complex may be crucial for virion trafficking [14] . As noted, nsp6 may initiate cellular autophagy and a general ER stress response also occurs during the formation of DMVs [95, 96] . Atg5 is necessary for the formation the crescent membranes and if is knocked out the yield of MHV is reduced although this is not a universal finding [97] . Although the precise mechanisms are ill defined, biological bilayers of proteins and lipids [98] are key to the separation and control of biological processes and their occurrence and composition is dynamic [99] . Bending, that is positive or negative membrane curvature, is driven by the acquisition and loss of peripheral membrane proteins, integral membrane proteins and by lipid composition [100, 101] . Membrane wrapping may occur around intrinsically curved proteins in which positively charged amino acids interact with negatively charged lipid head groups, for example, in the dynamin and BAR domain interactions, also known as scaffolding [102, 103] . Alternatively, crowding mechanisms may effect membrane curvature as a result of the asymmetric distribution of proteins either side of a cellular membrane [99, 104] , and the insertion of an amphipathic helix which can act as a wedge to expand one side of the membrane more than the other can also cause curvature as revealed by studies on influenza virus M2 protein, Epsins and Sar 1p [102, 105, 106] .