Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc

Plos Neglected Tropical Diseases

dc.creatorBarriga-Pinto, Gonzalo Andrés
dc.creatorVillalon-Leteli, Fernando
dc.creatorMarquez, Chantal L
dc.creatorBignon, Eduardo A
dc.creatorAcuña-Astudillo, Rodrigo Antonio
dc.creatorRoss, Breyan H
dc.creatorMonasterio, Octavio
dc.creatorMardones, Gonzalo A
dc.creatorVidal, Simon E
dc.creatorTischler-Dworschak, Nicole
dc.date2018-10-02T18:18:36Z
dc.date2022-07-07T15:19:37Z
dc.date2018-10-02T18:18:36Z
dc.date2022-07-07T15:19:37Z
dc.date2016
dc.date.accessioned2023-08-22T11:03:52Z
dc.date.available2023-08-22T11:03:52Z
dc.identifier1140050
dc.identifier1140050
dc.identifierhttps://hdl.handle.net/10533/220773
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8342496
dc.descriptionHantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses. Keywords. KeyWords Plus:VIRUS-MEMBRANE-FUSION; WEST-NILE-VIRUS; PROTEIN SECONDARY STRUCTURE; CIRCULAR-DICHROISM SPECTRA; BORNE ENCEPHALITIS-VIRUS; VALLEY FEVER VIRUS; ENVELOPE PROTEIN; DENGUE-VIRUS; HEMORRHAGIC-FEVER; RENAL SYNDROME
dc.languageeng
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relationinfo:eu-repo/grantAgreement//1140050
dc.relationinfo:eu-repo/semantics/dataset/hdl.handle.net/10533/93477
dc.relationhttps://www.ncbi.nlm.nih.gov/pubmed/27414047
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.titleInhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc
dc.titlePlos Neglected Tropical Diseases
dc.typeArticulo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion


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