Viral weapons of membrane destruction: variable modes of membrane penetration by non-enveloped viruses

Abstract

Significant progress has recently been obtained in our understanding of cellular entry by nonenveloped viruses (NEVs). A key step in the entry process involves the disruption or remodeling of the limiting cell membrane allowing the virus to gain access to the cellular replication machinery. Biochemical, genetic and structural data from diverse virus groups have shed light on the process of membrane penetration thereby revealing both the conservation and divergence of the mechanisms and principles governing this process. In general, membrane breach is achieved via the highly regulated spatiotemporal exposure of a virally-encoded membrane lytic factor, resulting in the transfer of the viral genome or nucleocapsid into the cytosol.

Dissecting Quasi-Equivalence in Nonenveloped Viruses: Membrane Disruption Is Promoted by Lytic Peptides Released from Subunit Pentamers, Not Hexamers

“…Chemical cues for activation of lytic activity (after cleavage has occurred) have been characterized for FHV, minor and major group rhinoviruses, parvovirus, polyomavirus, and adenovirus (20). In each case, acidic pH led to membrane disruption in vitro.…”

“…Following receptor attachment, nonenveloped viruses also enter through a variety of pathways but must cope with membrane translocation of their genomes without the aid of fusion. A common feature of many nonenveloped animal viruses is a capsid-associated lytic peptide that is activated by a chemical cue and assumed to facilitate membrane rupture for genome or particle delivery to the cytoplasm (1,20,31). This activity is commonly studied in vitro with artificial liposomes filled with a fluorescent dye that is quenched within the liposome but fluoresces strongly when the liposome is breached and the dye is released (2,16).…”

“…The first is part of the virus's maturation and is often an autocatalytic cleavage of a subunit polypeptide rendering the lytic peptide covalently independent but still associated with the particle. The second step occurs during infection, where the peptide activity is triggered by a chemical cue (usually a low pH) in a particular cellular compartment appropriate for the fissure of the associated membrane (20,22,31).…”

A Transmembrane Domain and GxxxG Motifs within L2 Are Essential for Papillomavirus Infection

“…Delivery of genetic material into the host cell is essential for viral infection, and the cellular membrane represents a major barrier which the nonenveloped viruses have evolved multiple ways to breach during infection (1,58). Papillomaviruses depend on the minor capsid protein L2, present at low abundance, to accomplish this task.…”

Uncoating of non-enveloped viruses

“…Since they are immobile they provide a holding force against the drifts exerted by CAR, and second, they induce conformational changes in the virus observed as untwisting of the penton base, which could loosen fiber-penton base interactions and facilitate fiber loss [64]. Although it is not known if protein VI exits through the 5-fold axis or elsewhere in the capsid, the externalization of protein VI is necessary for escape of the virus from endosomes [47,59,65]. In addition to the direct roles of ανβ3 or ανβ5 integrins in uncoating, integrin signalling may expose the virus to endosomal cues through the NPXY (asparagine-proline-any amino acidtyrosine) motive in β3 or β5, which recruits the adaptor complex AP-2 and facilitates endocytic uptake of virus [50,[66][67][68].…”