Retroviral Assembly and Budding Occur through an Actin-Driven Mechanism
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The assembly and budding of a new virus is a fundamental step in retroviral replication. Yet, despite substantial progress in the structural and biochemical characterization of retroviral budding, the underlying physical mechanism remains poorly understood, particularly with respect to the mechanism by which the virus overcomes the energy barrier associated with the formation of high membrane curvature during viral budding. Using atomic force, fluorescence, and transmission electron microscopy, we find that both human immunodeficiency virus and Moloney murine leukemia virus remodel the actin cytoskeleton of their host. These actin-filamentous structures assemble simultaneously with or immediately after the beginning of budding, and disappear as soon as the nascent virus is released from the cell membrane. Analysis of sections of cryopreserved virus-infected cells by transmission electron microscopy reveals similar actin filament structures emerging from every nascent virus. Substitution of the nucleocapsid domain implicated in actin binding by a leucine-zipper domain results in the budding of virus-like particles without remodeling of the cell's cytoskeleton. Notably, viruses carrying the modified nucleocapsid domains bud more slowly by an order of magnitude compared to the wild-type. The results of this study show that retroviruses utilize the cell cytoskeleton to expedite their assembly and budding.
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Actin-myosin interactions appear critical to formation of all four EV types, and phosphatidylserine translocation to the outer membrane is common to apoptotic bodies and microvesicles.
“For instance, actin-myosin interactions appear critical to the formation of all four types of EVs [66, 85, 100, 115].”
From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [85]
The Abstract (page unavailable) reports that actin remodeling helps retroviruses assemble and bud, supporting a limited connection between the cytoskeleton and particle formation. It does not establish that actin–myosin interactions are critical to formation of all four EV types; its myosin discussion describes earlier in vitro work, not a test of EV formation. The phosphatidylserine statement is not part of the supplied citing sentence and is not judged here. (LLM, conf=0.84)
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Cites
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Akers, J. C., Gonda, D., Kim, R., Carter, B. S., & Chen, C. C. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1084-8 · Cited by 1,423 · see citing works
“The most widely accepted mechanism for RLP formation involves interaction of retroviral proteins, such as Gag, with components of the plasma membrane [84] and cytoskeletal proteins [85].”
Budding of a Retrovirus: Some Assemblies Required
Rose, K. M., Hirsch, V. M., & Bouamr, F. (2020) · Viruses · doi:10.3390/v12101188 · Cited by 32 · see citing works
- Authors
- Gladnikoff, M., Shimoni, E., Gov, N. S., & Rousso, I.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Rousso, Itay
- Venue
- Biophysical Journal
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 97
- Issue
- 9
- Pages
- 2419-2428
- ISSN
- 0006-3495 (ISSN-L)
- PMC
- PMC2770610
- OpenAlex
- W2005872553
- Cited by
- 101
- References
- 1
- Citations by year
- 2026: 3 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 12 · 2013: 7 · 2012: 8
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biophysical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Israel Science Foundation (337/05)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- retroviral budding, viral assembly, actin cytoskeleton remodeling, membrane curvature, HIV-1, Moloney murine leukemia virus, nucleocapsid protein, leucine zipper domain, actin binding, virus-like particles, host-virus interaction
- MeSH terms
- Actins, Animals, Biophysics, Cytoskeleton, HeLa Cells, HIV, Humans, Microscopy, Fluorescence, Moloney murine leukemia virus, Retroviridae, Gene Products, gag, Microscopy, Atomic Force, NIH 3T3 Cells, Microscopy, Electron, Transmission, Mice
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