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      Paramyxovirus Glycoprotein Incorporation, Assembly and Budding: A Three Way Dance for Infectious Particle Production

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          Abstract

          Paramyxoviruses are a family of negative sense RNA viruses whose members cause serious diseases in humans, such as measles virus, mumps virus and respiratory syncytial virus; and in animals, such as Newcastle disease virus and rinderpest virus. Paramyxovirus particles form by assembly of the viral matrix protein, the ribonucleoprotein complex and the surface glycoproteins at the plasma membrane of infected cells and subsequent viral budding. Two major glycoproteins expressed on the viral envelope, the attachment protein and the fusion protein, promote attachment of the virus to host cells and subsequent virus-cell membrane fusion. Incorporation of the surface glycoproteins into infectious progeny particles requires coordinated interplay between the three viral structural components, driven primarily by the matrix protein. In this review, we discuss recent progress in understanding the contributions of the matrix protein and glycoproteins in driving paramyxovirus assembly and budding while focusing on the viral protein interactions underlying this process and the intracellular trafficking pathways for targeting viral components to assembly sites. Differences in the mechanisms of particle production among the different family members will be highlighted throughout.

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          A newly discovered human pneumovirus isolated from young children with respiratory tract disease

          From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional name for the newly discovered virus: human metapneumovirus. The clinical symptoms of the children from whom the virus was isolated were similar to those caused by human respiratory syncytial virus infection, ranging from upper respiratory tract disease to severe bronchiolitis and pneumonia. Serological studies showed that by the age of five years, virtually all children in the Netherlands have been exposed to human metapneumovirus and that the virus has been circulating in humans for at least 50 years.
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            A morbillivirus that caused fatal disease in horses and humans.

            A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
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              Influenza virus assembly and budding.

              Influenza A virus causes seasonal epidemics, sporadic pandemics and is a significant global health burden. Influenza virus is an enveloped virus that contains a segmented negative strand RNA genome. Assembly and budding of progeny influenza virions is a complex, multi-step process that occurs in lipid raft domains on the apical membrane of infected cells. The viral proteins hemagglutinin (HA) and neuraminidase (NA) are targeted to lipid rafts, causing the coalescence and enlargement of the raft domains. This clustering of HA and NA may cause a deformation of the membrane and the initiation of the virus budding event. M1 is then thought to bind to the cytoplasmic tails of HA and NA where it can then polymerize and form the interior structure of the emerging virion. M1, bound to the cytoplasmic tails of HA and NA, additionally serves as a docking site for the recruitment of the viral RNPs and may mediate the recruitment of M2 to the site of virus budding. M2 initially stabilizes the site of budding, possibly enabling the polymerization of the matrix protein and the formation of filamentous virions. Subsequently, M2 is able to alter membrane curvature at the neck of the budding virus, causing membrane scission and the release of the progeny virion. This review investigates the latest research on influenza virus budding in an attempt to provide a step-by-step analysis of the assembly and budding processes for influenza viruses. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                07 August 2014
                August 2014
                : 6
                : 8
                : 3019-3054
                Affiliations
                [1 ]Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536, USA; E-Mail: farah.najjar@ 123456uky.edu
                [2 ]Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA; E-Mail: aps13@ 123456psu.edu
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: rdutc2@ 123456uky.edu ; Tel.: +1-859-323-1795; Fax: +1-859-257-2283.
                Article
                viruses-06-03019
                10.3390/v6083019
                4147685
                25105277
                8732cf7c-5fe8-4f7c-b6f9-5137faf6190e
                © 2014 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 27 June 2014
                : 24 July 2014
                : 25 July 2014
                Categories
                Review

                Microbiology & Virology
                paramyxovirus,matrix protein,glycoproteins,virus assembly,viral trafficking,membrane rafts,virus budding

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