Paramyxovirus assembly and budding: building particles that transmit infections

Abstract

The paramyxoviruses define a diverse group of enveloped RNA viruses that includes a number of important human and animal pathogens. Examples include human respiratory syncytial virus and the human parainfluenza viruses, which cause respiratory illnesses in young children and the elderly; measles and mumps viruses, which have caused recent resurgences of disease in developed countries; the zoonotic Hendra and Nipah viruses, which have caused several outbreaks of fatal disease in Australia and Asia; and Newcastle disease virus, which infects chickens and other avian species. Like other enveloped viruses, paramyxoviruses form particles that assemble and bud from cellular membranes, allowing the transmission of infections to new cells and hosts. Here, we review recent advances that have improved our understanding of events involved in paramyxovirus particle formation. Contributions of viral matrix proteins, glycoproteins, nucleocapsid proteins, and accessory proteins to particle formation are discussed, as well as the importance of host factor recruitment for efficient virus budding. Trafficking of viral structural components within infected cells is described, together with mechanisms that allow for the selection of specific sites on cellular membranes for the coalescence of viral proteins in preparation of bud formation and virion release.

Figure 1. Budding of paramyxovirus particles

(A) Schematic illustration of paramyxovirus structural components that have assembled together on a cellular membrane, in preparation for budding. (B) Thin section of a Sendai virus-infected MDCK cell, visualized by electron microscopy. Arrows indicate individual sites from which virus budding has initiated on the apical cell surface. The nucleocapsid is observed aligning below the areas of curving membrane. (Adapted from Rodriguez-Boulan and Sabatini, 1978, with the author’s permission).

Figure 2. Paramyxovirus virions

(A) Schematic representation of a spherical paramyxovirus virion illustrating M protein lining the inner surface of the lipid envelope, the viral glycoproteins decorating the virion surface, and the helical RNP enclosed within. (B) A mumps virion purified by sucrose gradient centrifugation and imaged by transmission electron microscopy with negative staining. Glycoproteins are visible as a spike layer embedded in the envelope. (Adapted from Li et al., 2009, with the publisher’s permission).

Figure 3. Schematic illustration of a paramyxovirus life cycle

For details, refer to the text. Viral transcription and genome replication occur in the cytoplasm. Following their synthesis, viral structural proteins and RNPs assemble together at the infected cell plasma membrane for budding. Additional processes mediated by the viral accessory proteins (shown surrounded by brackets) are not illustrated.

Figure 4. Atomic structure of HRSV M protein

(A) Ribbon diagrams illustrating the similar beta-sheet arrangements of the HRSV M protein (blue) and Ebola virus VP40 (yellow) N-terminal domains. (B) Ribbon diagrams illustrating the similar beta-sheet arrangements of the HRSV M protein (red) and Ebola virus VP40 (cyan) C-terminal domains. (C) Space filling model of the HRSV M protein structure, with electrostatic surface potential depicted in colors ranging from red to blue. An extensive positively-charged (blue) surface is shown. (HRSV M protein PDB code 2VQP, Ebola virus VP40 PDB code 1ES6; figure adapted from Money et al., 2009, with the author’s permission).