10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Nipah virus induces two inclusion body populations: Identification of novel inclusions at the plasma membrane

      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

          Formation of cytoplasmic inclusion bodies (IBs) is a hallmark of infections with non-segmented negative-strand RNA viruses (order Mononegavirales). We show here that Nipah virus (NiV), a bat-derived highly pathogenic member of the Paramyxoviridae family, differs from mononegaviruses of the Rhabdo-, Filo- and Pneumoviridae families by forming two types of IBs with distinct localizations, formation kinetics, and protein compositions. IBs in the perinuclear region form rapidly upon expression of the nucleocapsid proteins. These IB peri are highly mobile and associate with the aggresome marker y-tubulin. IB peri can recruit unrelated overexpressed cytosolic proteins but do not contain the viral matrix (M) protein. Additionally, NiV forms an as yet undescribed IB population at the plasma membrane (IB PM) that is y-tubulin-negative but contains the M protein. Infection studies with recombinant NiV revealed that IB PM require the M protein for their formation, and most likely represent sites of NiV assembly and budding. The identification of this novel type of plasma membrane-associated IBs not only provides new insights into NiV biology and may open new avenues to develop novel antiviral approaches to treat these highly pathogenic viruses, it also provides a basis for a more detailed characterization of IBs and their role in virus assembly and replication in infections with other Mononegavirales.

          Author summary

          Inclusion bodies (IBs) induced by non-segmented negative-strand RNA viruses ( Mononegavirales) are described as mobile cytosolic compartments that concentrate viral proteins and represent the main viral replication sites in infected cells. This general concept is mainly based on studies with mononegaviruses from the Rhabdo-, Filo- and Pneumoviridae families. IBs induced by members of the Paramyxoviridae family are much less well characterized, and this study provides evidence that paramyxoviral IBs may have different compositions and functions. The main finding of this study is that Nipah virus (NiV), a highly pathogenic member of the genus Henipavirus in the family Paramyxoviridae, forms a novel type of IB whose formation at plasma membrane assembly sites depends on the viral matrix protein, and suggests a role for IBs not yet described for other Mononegavirales. This discovery clearly extents the current concept of IB functions and illustrates the need to further investigate IBs formed by other paramyxoviruses.

          Related collections

          Most cited references51

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

          Aggresomes: A Cellular Response to Misfolded Proteins

          Intracellular deposition of misfolded protein aggregates into ubiquitin-rich cytoplasmic inclusions is linked to the pathogenesis of many diseases. Why these aggregates form despite the existence of cellular machinery to recognize and degrade misfolded protein and how they are delivered to cytoplasmic inclusions are not known. We have investigated the intracellular fate of cystic fibrosis transmembrane conductance regulator (CFTR), an inefficiently folded integral membrane protein which is degraded by the cytoplasmic ubiquitin-proteasome pathway. Overexpression or inhibition of proteasome activity in transfected human embryonic kidney or Chinese hamster ovary cells led to the accumulation of stable, high molecular weight, detergent-insoluble, multiubiquitinated forms of CFTR. Using immunofluorescence and transmission electron microscopy with immunogold labeling, we demonstrate that undegraded CFTR molecules accumulate at a distinct pericentriolar structure which we have termed the aggresome. Aggresome formation is accompanied by redistribution of the intermediate filament protein vimentin to form a cage surrounding a pericentriolar core of aggregated, ubiquitinated protein. Disruption of microtubules blocks the formation of aggresomes. Similarly, inhibition of proteasome function also prevented the degradation of unassembled presenilin-1 molecules leading to their aggregation and deposition in aggresomes. These data lead us to propose that aggresome formation is a general response of cells which occurs when the capacity of the proteasome is exceeded by the production of aggregation-prone misfolded proteins.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Fatal encephalitis due to Nipah virus among pig-farmers in Malaysia.

            Between February and April, 1999, an outbreak of viral encephalitis occurred among pig-farmers in Malaysia. We report findings for the first three patients who died. Samples of tissue were taken at necropsy. Blood and cerebrospinal-fluid (CSF) samples taken before death were cultured for viruses, and tested for antibodies to viruses. The three pig-farmers presented with fever, headache, and altered level of consciousness. Myoclonus was present in two patients. There were signs of brainstem dysfunction with hypertension and tachycardia. Rapid deterioration led to irreversible hypotension and death. A virus causing syncytial formation of vero cells was cultured from the CSF of two patients after 5 days; the virus stained positively with antibodies against Hendra virus by indirect immunofluorescence. IgM capture ELISA showed that all three patients had IgM antibodies in CSF against Hendra viral antigens. Necropsy showed widespread microinfarction in the central nervous system and other organs resulting from vasculitis-induced thrombosis. There was no clinical evidence of pulmonary involvement. Inclusion bodies likely to be of viral origin were noted in neurons near vasculitic blood vessels. The causative agent was a previously undescribed paramyxovirus related to the Hendra virus. Close contact with infected pigs may be the source of the viral transmission. Clinically and epidemiologically the infection is distinct from infection by the Hendra virus. We propose that this Hendra-like virus was the cause of the outbreak of encephalitis in Malaysia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Negri bodies are viral factories with properties of liquid organelles

              Replication of Mononegavirales occurs in viral factories which form inclusions in the host-cell cytoplasm. For rabies virus, those inclusions are called Negri bodies (NBs). We report that NBs have characteristics similar to those of liquid organelles: they are spherical, they fuse to form larger structures, and they disappear upon hypotonic shock. Their liquid phase is confirmed by FRAP experiments. Live-cell imaging indicates that viral nucleocapsids are ejected from NBs and transported along microtubules to form either new virions or secondary viral factories. Coexpression of rabies virus N and P proteins results in cytoplasmic inclusions recapitulating NBs properties. This minimal system reveals that an intrinsically disordered domain and the dimerization domain of P are essential for Negri bodies-like structures formation. We suggest that formation of liquid viral factories by phase separation is common among Mononegavirales and allows specific recruitment and concentration of viral proteins but also the escape to cellular antiviral response.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Investigation
                Role: InvestigationRole: Supervision
                Role: Software
                Role: SupervisionRole: Writing – review & editing
                Role: Investigation
                Role: ConceptualizationRole: Supervision
                Role: ConceptualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Visualization
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Pathog
                PLoS Pathog
                plos
                plospath
                PLoS Pathogens
                Public Library of Science (San Francisco, CA USA )
                1553-7366
                1553-7374
                29 April 2019
                April 2019
                : 15
                : 4
                : e1007733
                Affiliations
                [1 ] Institute of Virology, Philipps University Marburg, Marburg, Germany
                [2 ] Division of Veterinary Medicine, Paul-Ehrlich-Institut, Langen, Germany
                University of Kentucky, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-4021-7728
                http://orcid.org/0000-0001-6908-1556
                http://orcid.org/0000-0002-9369-4050
                Article
                PPATHOGENS-D-18-02119
                10.1371/journal.ppat.1007733
                6488097
                31034506
                b63d398b-a717-4a7a-a616-afab1bd18ae7
                © 2019 Ringel et al

                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
                : 2 November 2018
                : 26 March 2019
                Page count
                Figures: 9, Tables: 0, Pages: 28
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: 197785619 - SFB 1021
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: MA 1886/6-2
                Award Recipient :
                Funded by: Jürgen-Manchot-Stiftung
                Award ID: Fellowship
                Award Recipient :
                This work was funded by grants from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) to AM (Projektnummer 197785619 - SFB 1021 and MA 1886/6-2). MR was supported by a fellowship of the Jürgen-Manchot-Stiftung. The funders had no role in 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 manuscript and its Supporting Information files.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article

                scite_
                0
                0
                0
                0
                Smart Citations
                0
                0
                0
                0
                Citing PublicationsSupportingMentioningContrasting
                View Citations

                See how this article has been cited at scite.ai

                scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.

                Similar content194

                Cited by23

                Most referenced authors554