Lipid–protein interactions in virus assembly and budding from the host cell plasma membrane

Motsa, Balindile B.; Stahelin, Robert V.

doi:10.1042/bst20200854

Cited by 19 publications

(16 citation statements)

References 52 publications

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“…We therefore conclude, based on our results and published work, that M binds to plasma membrane lipids as dimers and only forms higher-order oligomers during viral filament formation and VLPs budding. Similar results were shown also for other viral Matrix proteins, for example EBOV and MARV VP40 (42).…”

Section: Discussionsupporting

confidence: 85%

Specific targeting and clustering of Phosphatidylserine lipids by RSV M protein is critical for virus particle production

Swain

Bierre

Veyrie

et al. 2023

Preprint

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Human Respiratory Syncytial virus (RSV) is the leading cause of infantile bronchiolitis in the developed world and of childhood deaths in resource-poor settings. The elderly and the immunosuppressed are also affected. It is a major unmet target for vaccines and anti-viral drugs. RSV assembles and buds from the host cell plasma membrane by forming infections viral particles which are mostly filamentous. A key interaction during RSV assembly is the interaction of plasma membrane lipids with the Matrix (M) protein layer forming at assembly sites. Although the structure of RSV M protein dimer is known, it is unclear how the viral M proteins interact with certain plasma membrane lipids to promote viral assembly. Here, we demonstrate that M proteins cluster at the plasma membrane by selectively binding with phosphatidylserine (PS). Our in vitro studies suggest that M binds PS lipid as dimers and M mutant with a phosphomimetic substitution inhibits interaction with PS lipids. The presence of other negatively charged lipids like PI(4, 5)P2 does not affect RSV M ability to bind, while cholesterol negatively affects M interaction with lipids. Moreover, we show that the initial binding of the RSV M protein with lipids is independent of the cytoplasmic tail of fusion (F) glycoprotein (FCT). It is the first in vitro study of M interaction with plasma membrane lipids. M binding to plasma membrane may represent a viable therapeutic strategy for small molecules that will block viral spread.

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Section: Discussionsupporting

confidence: 85%

Specific targeting and clustering of Phosphatidylserine lipids by RSV M protein is critical for virus particle production

Swain

Bierre

Veyrie

et al. 2023

Preprint

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show abstract

“…It is firmly established that VP40, the major Ebola Matrix protein, regulates virus assembly and egress at the inner leaflet of the host-cell plasma membrane by recognizing PS [ 10 ]. To identify the VP40 amino acids involved in membrane recognition, Adu-Gyamfi et al generated several VP40 protein mutants and monitored their capacity to penetrate Langmuir monolayers by measuring changes in the monolayers’ lateral pressure.…”

Section: Artificial Lipid Membranes As Tools For Viral Assembly Researchmentioning

confidence: 99%

“…At the same time, via its nucleocapsid domain, Gag particles also interact with its viral RNA genome, and both phenomena lead to the formation of the nucleus for subsequent Gag protein assembly [ 7 , 8 ]. In the case of IAV, the protein M1, and for EBOV, the protein VP40 are both known to mainly interact with phosphatidylserine (PS) at the inner leaflet of the PM [ 9 , 10 ] ( Figure 1 B).…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the Assembly of Enveloped Viruses Using Model Lipid Membranes

2022

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The cell plasma membrane is mainly composed of phospholipids, cholesterol and embedded proteins, presenting a complex interface with the environment. It maintains a barrier to control matter fluxes between the cell cytosol and its outer environment. Enveloped viruses are also surrounded by a lipidic membrane derived from the host-cell membrane and acquired while exiting the host cell during the assembly and budding steps of their viral cycle. Thus, model membranes composed of selected lipid mixtures mimicking plasma membrane properties are the tools of choice and were used to decipher the first step in the assembly of enveloped viruses. Amongst these viruses, we choose to report the three most frequently studied viruses responsible for lethal human diseases, i.e., Human Immunodeficiency Type 1 (HIV-1), Influenza A Virus (IAV) and Ebola Virus (EBOV), which assemble at the host-cell plasma membrane. Here, we review how model membranes such as Langmuir monolayers, bicelles, large and small unilamellar vesicles (LUVs and SUVs), supported lipid bilayers (SLBs), tethered-bilayer lipid membranes (tBLM) and giant unilamellar vesicles (GUVs) contribute to the understanding of viral assembly mechanisms and dynamics using biophysical approaches.

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“…Because PtdSer can induce membrane curvature, it is likely that PtdSer scrambling in the plasma membrane promotes the egress of enveloped viruses. Curiously, EBOV matrix protein VP40 must first bind to inner leaflet PtdSer during particle assembly, followed by PtdSer exposure [53]. Thus, it will be interesting to examine the exact stimuli leading to scramblase activation and how this timing is achieved to enhance particle budding.…”

Section: Scramblase Xkr8 and Viral Buddingmentioning

confidence: 99%

Scrambled or flipped: 5 facts about how cellular phosphatidylserine localization can mediate viral replication

Acciani

Brindley

2022

PLoS Pathog

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Lipid–protein interactions in virus assembly and budding from the host cell plasma membrane

Cited by 19 publications

References 52 publications

Specific targeting and clustering of Phosphatidylserine lipids by RSV M protein is critical for virus particle production

Specific targeting and clustering of Phosphatidylserine lipids by RSV M protein is critical for virus particle production

Deciphering the Assembly of Enveloped Viruses Using Model Lipid Membranes

Scrambled or flipped: 5 facts about how cellular phosphatidylserine localization can mediate viral replication

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