Physical Aspects of Viral Membrane Fusion

Abstract

Enveloped viruses commonly employ membrane fusion during cell penetration in order to deliver their genetic material across the cell boundary. Large conformational changes in the proteins embedded in the viral membrane play a fundamental role in the membrane fusion process. Despite the tremendously wide variety of viruses that contain membranes, it appears that they all contain membrane fusion protein machinery with a remarkably conserved mechanism of action. Much of our current biochemical understanding of viral membrane fusion has been derived from high-resolution structural studies and solution-based in vitro assays in which viruses fuse with liposomes or cells. Recently, single-particle experiments have been used to provide measurements of details not available in the bulk assays. Here we focus our discussion on the key dynamical aspects of fusion protein structure, along with some of the experimental and computational techniques presently being used to investigate viral-mediated membrane fusion.

Visualization of the moment of mouse sperm–egg fusion and dynamic localization of IZUMO1

“…Recent experiments using variously prepared unilamellar liposomes have clarified fundamental physicochemical questions in fusion (Brunger et al, 2009;Wessels and Weninger, 2009). Essential factors are also emerging using gene knockout approaches in studies on muscle cell fusion (Abmayr and Pavlath, 2012;Chen, 2011;Powell and Wright, 2011), syncytial formation in the placenta (Dupressoir et al, 2011), fusogens in epithelia and muscle cells in Caenorhabditis elegans (Sapir et al, 2007), and fertilization in nematodes, plants, protists and mammals (Hirai et al, 2008;Ikawa et al, 2010;Nishimura and L'Hernault, 2010), but the mechanisms involved in cell-cell fusion are still not fully explainable on a molecular basis.…”

Sensing-Applications of Surface-Based Single Vesicle Arrays

“…A new promising application of the single vesicle platform has emerged in the study of biological membrane fusion reactions as encountered, e.g., in the secretory pathway of eukaryotic cells [ 51 ], neurotransmission [ 52 ] and virus infection [ 53 ]. The merging of the membrane of a transport vesicle or virus particle with a cellular target membrane is acentral step in all these pathways.…”

In and Out — Biochemical and Biophysical Mechanisms of Viral Fusion and Assembly

“…In this special issue dedicated to the Biochemical and Biophysical Mechanisms of Viral Fusion and Assembly, the review article by Wessels and Weninger [1] is centered on the entry of enveloped viruses (such as influenza virus or HIV) onto a target cell, describing the two viral players on this process: viral membrane proteins and lipids. Large conformational changes in the proteins embedded in the viral membrane play a fundamental role in the membrane fusion process.…”

“…While Wessels and Weninger dealt with the entry of enveloped virus onto a target cell [1], Ruiz et al [2] focused on the cellular entry of rotavirus (a nonenveloped virus), following a complex multistep process in which different domains of the rotavirus surface proteins interact with different cell surface molecules, which act as putative receptors on the plasma membrane. Beside the different aspects of rotavirus entry (viral structure, cell receptors, penetration, permeabilization, membrane interaction, and endocytosis), the article integrates the knowledge of other steps of the viral life cycle; namely, replication and assembly.…”

“…While the previously mentioned articles in this special issue deal mainly with the entry of the viral content onto a target cell [1,2,6], the article by José L. Neira [9] is focused on one of the key players of the HIV assembly process -the capsid protein. The ordered oligomerization of several hundred copies of this protein constitutes the scaffold for the new virion formation, enclosing the viral RNA and other proteins.…”