Virus maturation by budding - PubMed (original) (raw)

Review

Virus maturation by budding

H Garoff et al. Microbiol Mol Biol Rev. 1998 Dec.

Abstract

Enveloped viruses mature by budding at cellular membranes. It has been generally thought that this process is driven by interactions between the viral transmembrane proteins and the internal virion components (core, capsid, or nucleocapsid). This model was particularly applicable to alphaviruses, which require both spike proteins and a nucleocapsid for budding. However, genetic studies have clearly shown that the retrovirus core protein, i.e., the Gag protein, is able to form enveloped particles by itself. Also, budding of negative-strand RNA viruses (rhabdoviruses, orthomyxoviruses, and paramyxoviruses) seems to be accomplished mainly by internal components, most probably the matrix protein, since the spike proteins are not absolutely required for budding of these viruses either. In contrast, budding of coronavirus particles can occur in the absence of the nucleocapsid and appears to require two membrane proteins only. Biochemical and structural data suggest that the proteins, which play a key role in budding, drive this process by forming a three-dimensional (cage-like) protein lattice at the surface of or within the membrane. Similarly, recent electron microscopic studies revealed that the alphavirus spike proteins are also engaged in extensive lateral interactions, forming a dense protein shell at the outer surface of the viral envelope. On the basis of these data, we propose that the budding of enveloped viruses in general is governed by lateral interactions between peripheral or integral membrane proteins. This new concept also provides answers to the question of how viral and cellular membrane proteins are sorted during budding. In addition, it has implications for the mechanism by which the virion is uncoated during virus entry.

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Figures

FIG. 1

Replication of naked and enveloped viruses in eucaryotic cells.

FIG. 2

Viral proteins that drive budding. (I) Spike (red)- and NC (blue)-dependent budding of alphaviruses. (IIa) Gag protein-driven budding of a type C retrovirus. The membrane is shown in yellow, and the submembrane layer of Gag protein is depicted in blue. An RNA molecule (green) is also indicated, but it is unclear whether this is necessary for budding. (IIb) Budding of a type D retrovirus “Gag” particle. In this case, Gag molecules are assembled into a complete core in the cytoplasm prior to membrane attachment. (III) M (red, unfilled) and E (red, filled) membrane protein-driven budding of coronavirus. (IV) Rhabdovirus budding is depicted as an efficient (left) or inefficient (right) process depending on the presence of the spike proteins (red). The M protein layer below the membrane is shown in brown, and the RNP is depicted as a green helix with proteins (blue).

FIG. 3

Reconstruction of an alphavirus (RRV) particle from cryo-EM analysis and image processing. (A) Three-dimensional surface structure of the virion (diameter, ∼70 nm) viewed along an icosahedral threefold axis. The spikes ([E1-E2]3), located at the threefold and quasi-threefold axes, have a flower-like head with three bilobal petals. The spikes are engaged in extensive lateral interactions close to the lipid bilayer via their skirts. These parts of the spikes are colored bluish. The lipid bilayer (yellow) is seen through openings in the spike-skirt protein layer at the twofold and fivefold symmetry axes. (B) Depth-cued representation of the structure in panel A. Blue lines indicating the T = 4 lattice are superimposed. (C) Schematic representation of the interactions between the spikes (green) at the threefold (circled 3) or quasi-threefold (circled Q3) axes and the C molecules (yellow) of the capsomers in the underlying NC. (D) Depth-cued representation of the three-dimensional structure of the NC viewed along an icosahedral threefold axis. The COOH-terminal protease domains of the C molecules form hexameric and pentameric capsomers at the twofold and fivefold axes. Red lines indicating the T = 4 lattice are superimposed. Modified from reference with permission of the publisher.

FIG. 4

MA protein trimers organized in a hexameric lattice. The MA protein monomers are shown as red, blue, and green polypeptide chain drawings. They form trimeric clusters in a hexameric lattice. One hexameric ring is indicated by the dashed line. The center-to-center distance between neighboring hexameric rings is 68 Å. Modified from reference with permission.

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Virus maturation by budding - PubMed (original) (raw)