Identification and Characteristics of Fusion Peptides Derived From Enveloped Viruses

Abstract

Membrane fusion events allow enveloped viruses to enter and infect cells. The study of these processes has led to the identification of a number of proteins that mediate this process. These proteins are classified according to their structure, which vary according to the viral genealogy. To date, three classes of fusion proteins have been defined, but current evidence points to the existence of additional classes. Despite their structural differences, viral fusion processes follow a common mechanism through which they exert their actions. Additional studies of the viral fusion proteins have demonstrated the key role of specific proteinogenic subsequences within these proteins, termed fusion peptides. Such peptides are able to interact and insert into membranes for which they hold interest from a pharmacological or therapeutic viewpoint. Here, the different characteristics of fusion peptides derived from viral fusion proteins are described. These criteria are useful to identify new fusion peptides. Moreover, this review describes the requirements of synthetic fusion peptides derived from fusion proteins to induce fusion by themselves. Several sequences of the viral glycoproteins E1 and E2 of HCV were, for example, identified to be able to induce fusion, which are reviewed here.

The Cellular Characterization of SARS-CoV-2 Spike Protein in Virus-Infected Cells Using the Receptor Binding Domain Binding Specific Human Monoclonal Antibodies

“…In this context, high-resolution structures of the S protein on isolated SARS-CoV-2 particles have demonstrated that low levels of the S protein trimer disassociate, leaving the S2 domain radiating from the virus envelope in an extended postfusion conformation ( 34 ). It is possible that the freely exposed fusion peptide at the N terminus of the S2 protein may insert into the plasma membrane on infected cells and serve as an alternative transmembrane domain ( 35 ). In such a scenario, this would tether the virus particles to the surface of infected cells and facilitate the localized cell-to-cell spread of infection that we observe.…”

The cellular characterisation of SARS-CoV-2 spike protein in virus-infected cells using Receptor Binding Domain-binding specific human monoclonal antibodies

“…In this context, high resolution structures of the S protein on isolated SARS-CoV-2 particles have demonstrated that low levels of the S protein trimer disassociate leaving the S2 domain radiating from the virus envelope in an extended post-fusion conformation [39]. It is possible that the freely exposed fusion peptide at the N-terminus of the S2 protein may insert into the plasma membrane on infected cells and serve as an alternative transmembrane domain [40]. In such a scenario, this would tether the virus particles to the surface of infected cells and facilitate the localized cell-to cell spread of infection that we observe.…”

“…It is possible that the freely exposed fusion peptide at the N-terminus of the S2 protein may insert into the plasma membrane on infected cells and serve as an alternative transmembrane domain [40]. In such a scenario, this would tether the virus particles to the surface of infected cells and facilitate the localized cell-to cell spread of infection that we observe.…”

Unique Structure and Distinctive Properties of the Ancient and Ubiquitous Gamma-Type Envelope Glycoprotein

“…Retrovirus Envs are class I fusion proteins, with fusion peptides (FP) located at or near the N-terminus of TM [ 126 , 127 ]. Gamma-type Env can have N-terminal FP, as is found in most gammaretroviruses and deltaretroviruses, or the FP can comprise an internal “loop” near the N-terminus of TM demarcated by disulfide bonded cysteines, as is the case for alpharetroviruses [ 100 ].…”