46
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Dual Mutation Events in the Haemagglutinin-Esterase and Fusion Protein from an Infectious Salmon Anaemia Virus HPR0 Genotype Promote Viral Fusion and Activation by an Ubiquitous Host Protease

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          In Infectious salmon anaemia virus (ISAV), deletions in the highly polymorphic region (HPR) in the near membrane domain of the haemagglutinin-esterase (HE) stalk, influence viral fusion. It is suspected that selected mutations in the associated Fusion (F) protein may also be important in regulating fusion activity. To better understand the underlying mechanisms involved in ISAV fusion, several mutated F proteins were generated from the Scottish Nevis and Norwegian SK779/06 HPR0. Co-transfection with constructs encoding HE and F were performed, fusion activity assessed by content mixing assay and the degree of proteolytic cleavage by western blot. Substitutions in Nevis F demonstrated that K276 was the most likely cleavage site in the protein. Furthermore, amino acid substitutions at three sites and two insertions, all slightly upstream of K276, increased fusion activity. Co-expression with HE harbouring a full-length HPR produced high fusion activities when trypsin and low pH were applied. In comparison, under normal culture conditions, groups containing a mutated HE with an HPR deletion were able to generate moderate fusion levels, while those with a full length HPR HE could not induce fusion. This suggested that HPR length may influence how the HE primes the F protein and promotes fusion activation by an ubiquitous host protease and/or facilitate subsequent post-cleavage refolding steps. Variations in fusion activity through accumulated mutations on surface glycoproteins have also been reported in other orthomyxoviruses and paramyxoviruses. This may in part contribute to the different virulence and tissue tropism reported for HPR0 and HPR deleted ISAV genotypes.

          Related collections

          Most cited references84

          • Record: found
          • Abstract: found
          • Article: not found

          Structures and mechanisms of viral membrane fusion proteins: multiple variations on a common theme.

          Recent work has identified three distinct classes of viral membrane fusion proteins based on structural criteria. In addition, there are at least four distinct mechanisms by which viral fusion proteins can be triggered to undergo fusion-inducing conformational changes. Viral fusion proteins also contain different types of fusion peptides and vary in their reliance on accessory proteins. These differing features combine to yield a rich diversity of fusion proteins. Yet despite this staggering diversity, all characterized viral fusion proteins convert from a fusion-competent state (dimers or trimers, depending on the class) to a membrane-embedded homotrimeric prehairpin, and then to a trimer-of-hairpins that brings the fusion peptide, attached to the target membrane, and the transmembrane domain, attached to the viral membrane, into close proximity thereby facilitating the union of viral and target membranes. During these conformational conversions, the fusion proteins induce membranes to progress through stages of close apposition, hemifusion, and then the formation of small, and finally large, fusion pores. Clearly, highly divergent proteins have converged on the same overall strategy to mediate fusion, an essential step in the life cycle of every enveloped virus.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Protein-lipid interplay in fusion and fission of biological membranes.

            Disparate biological processes involve fusion of two membranes into one and fission of one membrane into two. To formulate the possible job description for the proteins that mediate remodeling of biological membranes, we analyze the energy price of disruption and bending of membrane lipid bilayers at the different stages of bilayer fusion. The phenomenology and the pathways of the well-characterized reactions of biological remodeling, such as fusion mediated by influenza hemagglutinin, are compared with those studied for protein-free bilayers. We briefly consider some proteins involved in fusion and fission, and the dependence of remodeling on the lipid composition of the membranes. The specific hypothetical mechanisms by which the proteins can lower the energy price of the bilayer rearrangement are discussed in light of the experimental data and the requirements imposed by the elastic properties of the bilayer.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.

              The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 October 2015
                2015
                : 10
                : 10
                : e0142020
                Affiliations
                [1 ]Aquaculture and Fish Health, Marine Scotland Science, Aberdeen, United Kingdom
                [2 ]Epidemiology, Norwegian Veterinary Institute, Oslo, Norway
                [3 ]School of Biological Sciences, University of Aberdeen, Aberdeen, United Kingdom
                St. Jude Children's Research Hospital, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MF TM KF AM BC. Performed the experiments: MF KL. Analyzed the data: MF KL. Contributed reagents/materials/analysis tools: AM BC CS. Wrote the paper: MF KL TM KF CS AM BC.

                Article
                PONE-D-15-38391
                10.1371/journal.pone.0142020
                4627773
                26517828
                cba8c0ac-29b7-47b8-8805-e1c71a2b292c
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 31 August 2015
                : 15 October 2015
                Page count
                Figures: 5, Tables: 3, Pages: 19
                Funding
                The Scottish Government funded this work, as part of their global budget on aquaculture research. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article