Three-Dimensional Analysis of Budding Sites and Released Virus Suggests a Revised Model for HIV-1 Morphogenesis
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Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release--akin to its role in vesicle formation--and is not restricted to severing the thin membrane tether.
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A mature HIV-1 virion contains approximately 120 copies of integrase protein.
“It is estimated that a mature HIV-1 virion contains about 120 copies of IN protein8,9.”
From Structure and function of retroviral integrase (2022) · cites this paper as [9]
Coreceptor binding triggers conformational changes and dissociation of the gp120-gp41 heterotrimer, helping gp41 penetrate the plasma membrane and facilitating fusion of the viral envelope with the plasma membrane, depositing the CA containing viral genetic material into the host cell cytoplasm.
“Coreceptor binding triggers further conformational changes and dissociation of the trimer of gp120–gp41 heterotrimer. This dissociation helps gp41 penetrate the plasma membrane, facilitating fusion of the viral envelope with the plasma membrane, allowing the deposition of the CA containing the viral genetic material into the cytoplasm of the host cell (Carlson et al. 2008, Blumenthal et al. 2012).”
From Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication (2026) · cites this paper as Carlson et al. 2008
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- Authors
- Carlson, L.-A., Briggs, J. A. G., Glass, B., Riches, J. D., Simon, M. N., Johnson, M. C., Müller, B., Grünewald, K., & Kräusslich, H.-G.
- Affiliations
- University Hospital Heidelberg (DE)
- European Molecular Biology Laboratory (DE)
- Brookhaven National Laboratory (US)
- University of Missouri (US)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Grünewald, Kay
- Kräusslich, Hans-Georg
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 4
- Issue
- 6
- Pages
- 592-599
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3454483
- OpenAlex
- W2041321679
- Cited by
- 230
- References
- 35
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 9 · 2023: 9 · 2022: 16 · 2021: 7 · 2020: 15 · 2019: 14 · 2018: 10 · 2017: 14 · 2016: 16 · 2015: 15 · 2014: 11 · 2013: 15 · 2012: 21
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1725 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI073098)
- National Institute of Biomedical Imaging and Bioengineering (5 P41 EB2181, P41EB002181)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- viral budding, ESCRT machinery, virion morphology, electron tomography, scanning transmission electron microscopy
- MeSH terms
- Cell Line, Cell Membrane, HeLa Cells, Humans, Microscopy, Electron, Scanning, Models, Molecular, Virion, HIV-1, Virus Assembly, Microscopy, Electron, Transmission, gag Gene Products, Human Immunodeficiency Virus
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