Membrane binding proteins of coronaviruses

J Alsaadi, Entedar A; Jones, Ian M

During assembly, all enveloped viruses face the challenge of combining capsids proteins and genome produced in the cytosol with glycoproteins that predominantly occur in another cellular compartment, the luminal side of the ER. A cell membrane separates these components and must be breached or used in the assembly of the complete virion and this is achieved in three stages ( Figure 2) . First, the virus proteins coalesce on the membrane, capsid proteins grouping together underneath the patch of membrane where viral glycoproteins are embedded. Second, the membrane bulges outward to form a bud decorated by the viral transmembrane proteins and enclosing the capsid proteins and genome. Third and finally, the bud splits from the rest of the membrane by scission, a pinching-off at the base which releases the virion either into an intracellular vesicle as in the case for CoVs or directly out of the cell [1] . For many enveloped viruses these processes are actioned by viral protein interaction with host proteins of the endosomal sorting complexes required for transport (ESCRT) machinery [107] . Surprisingly however, perhaps because of incompatibility with the extensive membrane rearrangements induced in infected cells, CoVs appear not to use ESCRT proteins for egress, rather the S protein has a signal for ERGIC retention in its cytoplasmic tail [108] while the M protein locates to the ERGIC and cis-Golgi via its first TM domain where it also oligomerises [109] to drive the budding process. M-N interactions ensure that the viral RNPs also occur at these budding sites allowing the budding virus to incorporate a copy of the new genome [46, 110] . The E protein, as a viroporin, has been implicated in membrane scission as E is present in virus particles at only a very low level and most is left associated with the ERGIC and cis Golgi consistent with a predominant role as a mediator of virus assembly and release at this location [111] . The lipid content at these locations may also enhance virus budding [112, 113] .