Hantavirus Gn and Gc envelope glycoproteins: key structural units for virus cell entry and virus assembly - PubMed (original) (raw)

Review

Hantavirus Gn and Gc envelope glycoproteins: key structural units for virus cell entry and virus assembly

Nicolás Cifuentes-Muñoz et al. Viruses. 2014.

Abstract

In recent years, ultrastructural studies of viral surface spikes from three different genera within the Bunyaviridae family have revealed a remarkable diversity in their spike organization. Despite this structural heterogeneity, in every case the spikes seem to be composed of heterodimers formed by Gn and Gc envelope glycoproteins. In this review, current knowledge of the Gn and Gc structures and their functions in virus cell entry and exit is summarized. During virus cell entry, the role of Gn and Gc in receptor binding has not yet been determined. Nevertheless, biochemical studies suggest that the subsequent virus-membrane fusion activity is accomplished by Gc. Further, a class II fusion protein conformation has been predicted for Gc of hantaviruses, and novel crystallographic data confirmed such a fold for the Rift Valley fever virus (RVFV) Gc protein. During virus cell exit, the assembly of different viral components seems to be established by interaction of Gn and Gc cytoplasmic tails (CT) with internal viral ribonucleocapsids. Moreover, recent findings show that hantavirus glycoproteins accomplish important roles during virus budding since they self-assemble into virus-like particles. Collectively, these novel insights provide essential information for gaining a more detailed understanding of Gn and Gc functions in the early and late steps of the hantavirus infection cycle.

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Figures

Figure 1

Schematic Representation of Hantavirus Particles. (A) Representation of TULV and HTNV particles. Surface spike organizations are based on the cryo-ET maps of each virus. (B) Amplified view of the spike arrangements of HTNV and TULV represented in (A). Spike projections were drawn based on a vertical slice through the volume of the electron density of cryo-ET maps obtained by Huiskonen and colleagues [17] and Battisti and colleagues [16], respectively. The maps were downloaded from EMDataBank, accession numbers 1704 (TULV) and 2056 (HTNV) and surface projections rendered in the Chimera program [18].

Figure 2

Functions of Hantavirus Envelope Glycoproteins during Virus Life Cycle. Once hantavirus particles attach to cell surface receptors by one, or both glycoproteins (1) they are uptaken by clathrin-mediated endocytosis (2a) or alternatively by other pathways that do not involve clathrin (2b). After virus particle uptake, the viral glycoproteins dissociate at one point from cellular receptors (3). Virus particles traffic down through the endocytic pathway until the low pH of endosomes, and possibly other cellular factors, trigger the Gc-mediated virus-cell membrane fusion process, releasing RNCs to the cytosol (4). After the transcription/replication of the viral genome and the synthesis of new viral proteins have taken place (5), the glycoproteins accumulate at internal membranes, where they can mediate virus assembly and budding (6a) and egress through the secretory pathway (7). Alternatively, new viruses may assemble and bud directly from the plasma membrane (6b). E.E. indicates early endosome, L.E. indicates late endosome.

Figure 3

Schematic Representation of Hantavirus Glycoprotein Processing and Functions. The Gn (dark cyan) and Gc (light cyan) glycoprotein ectodomains, transmembrane regions and endodomains are represented according to their location relative to the membrane (horizontal grey line). The Signal peptide (SP) and WAASA sequences indicate the cleavage sites within GPC. N represents the location of asparagine residues that are likely to carry glycosylations; the numbers following these letters indicate the corresponding residue number within GPC of ANDV. ZF 1 + 2 indicates the location of the two zinc finger domains, RNC-BS indicates the suggested ribonucleocapsid binding sites. The motif YxxL represents residues involved in ubiquitination. FL indicates the location of the putative fusion loop of ANDV Gc. The molecular structure of the ANDV Gn-CT zinc finger domains (dark cyan) was obtained from the NCBI databank, PDBid: 2K9H [24]. The molecular model for the ANDV Gc fusion protein ectodomain was developed previously [29]. All ribbon diagramsof molecular structures were rendered in the PyMOL Molecular Graphics System [61].

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Hantavirus Gn and Gc envelope glycoproteins: key structural units for virus cell entry and virus assembly - PubMed (original) (raw)