Mathematical determination of the HIV-1 matrix shell structure and its impact on the biology of HIV-1
Open accessAbstract
Since its discovery in the early 1980s, there has been significant progress in understanding the biology of type 1 human immunodeficiency virus (HIV-1). Structural biologists have made tremendous contributions to this challenge, guiding the development of current therapeutic strategies. Despite our efforts, there are unresolved structural features of the virus and consequently, significant knowledge gaps in our understanding. The superstructure of the HIV-1 matrix (MA) shell has not been elucidated. Evidence by various high-resolution microscopy techniques support a model composed of MA trimers arranged in a hexameric configuration consisting of 6 MA trimers forming a hexagon. In this manuscript we review the mathematical limitations of this model and propose a new model consisting of a 6-lune hosohedra structure, which aligns with available structural evidence. We used geometric and rotational matrix computation methods to construct our model and predict a new mechanism for viral entry that explains the increase in particle size observed during CD4 receptor engagement and the most common HIV-1 ellipsoidal shapes observed in cryo-EM tomograms. A better understanding of the HIV-1 MA shell structure is a key step towards better models for viral assembly, maturation and entry. Our new model will facilitate efforts to improve understanding of the biology of HIV-1.
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The number of Gag molecules (about 2,000 per nascent particle) exceeds the smaller number of Env trimers (about 10 per virion).
“even though the number of Gag molecules (about 2,000 per nascent particle 56 ) exceeds the smaller number of Env trimers (about 10 per virion). 57”
From Revealing viral and cellular dynamics of HIV-1 at the single-cell level during early treatment periods (2023) · cites this paper as [56]
The Introduction (page unavailable) reports an estimate of 2,000–5,000 MA monomers per mature HIV-1 particle, supporting the approximate scale of the cited Gag count. It does not give about 2,000 Gag molecules per nascent particle. The separate Env-trimer count is attached to citation 57, not this source. (LLM, conf=0.83)
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Self-citation
- Authors
- Sun, W., Reyes-Serratos, E., Barilla, D., Santos, J. R. L., Bujold, M., Graves, S., & Marcet-Palacios, M.
- Affiliations
- University of Alberta (CA)
- Northern Alberta Institute of Technology (CA)
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2019-11-12
- Volume
- 14
- Issue
- 11
- Pages
- e0224965
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC6850549
- OpenAlex
- W2987258980
- Cited by
- 6
- References
- 30
- Citations by year
- 2024: 1 · 2023: 3 · 2021: 2
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Alberta Innovates - Technology Futures (G2015000484)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- HIV-1, viral entry mechanism, viral particle size
- MeSH terms
- Models, Molecular, Peptides, Viral Matrix Proteins, Virion, HIV-1, Virus Assembly
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