Host cell entry by influenza and other enveloped viruses is well characterized, however, the manner in which non-enveloped viruses deliver their genome across host cell membranes in the absence of membrane fusion remains unresolved. The discovery of short, membrane altering, amphipathic or hydrophobic sequences in several non-enveloped virus capsid proteins such as the γ (gamma) peptide of nodaviruses and tetraviruses, VP4 and the N-terminal region of VP1 of picornaviruses, μ1N of reoviruses, and protein VI of adenoviruses suggests that these small peptides facilitate breaching of the host membrane and the delivery of the viral genome into the host cell. In spite of conspicuous differences in entry among non-enveloped virions, the short stretches of membrane active regions are associated with similar, entry-related events including: i) proteolytic cleavage of a precursor capsid protein resulting in increased dynamic character and/or accessibility of these peptides; ii) structural changes in the virus capsid triggered by receptor binding and/or low pH in entry compartments, resulting in peptide exposure; iii) externalized peptides interact with host membranes and disrupt them, facilitating delivery of the viral genome inside the host cell. Here we discuss the membrane alteration activity in nonenveloped viruses with reference to the γ peptide of nodaviruses. Virtually all of the characteristics of γ are shared by analogous peptides in other non-enveloped viruses, making it a simple prototype for comparative purposes.
Keywords: Virus, non-enveloped, peptide, amphipathic helix, hydrophobic, entry, membrane, penetration, capsid, flock house virus, proteolytic cleavage, dynamic, accessibility, endosome, receptor binding, conformation, exposure, disruption, fusion, autocatalytic.