{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:01:18Z","timestamp":1760148078697,"version":"build-2065373602"},"reference-count":22,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Sciences and Engineering Research Council of Canada (NSERC)","award":["DGECR-2020-00015"],"award-info":[{"award-number":["DGECR-2020-00015"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The molecular structure of the type 1 human immunodeficiency virus (HIV-1) is tightly linked to the mechanism of viral entry. The spike envelope (Env) glycoproteins and their interaction with the underlying matrix (MA) shell have emerged as key components of the entry mechanism. Microscopy evidence suggests that the MA shell does not span the entire inner lipid surface of the virus, producing a region of the virus that completely lacks an MA shell. Interestingly, evidence also suggests that Env proteins cluster during viral maturation and, thus, it is likely that this event takes place in the region of the virus that lacks an MA shell. We have previously called this part of the virus a fusion hub to highlight its importance during viral entry. While the structure of the MA shell is in contention due to the unaddressed inconsistencies between its reported hexagonal arrangement and the physical plausibility of such a structure, it is possible that a limited number of MA hexagons could form. In this study, we measured the size of the fusion hub by analysing the cryo-EM maps of eight HIV-1 particles and measured the size of the MA shell gap to be 66.3 nm \u00b1 15.0 nm. We also validated the feasibility of the hexagonal MA shell arrangement in six reported structures and determined the plausible components of these structures that do not violate geometrical limitations. We also examined the cytosolic domain of Env proteins and discovered a possible interaction between adjacent Env proteins that could explain the stability of cluster formation. We present an updated HIV-1 model and postulate novel roles of the MA shell and Env structure.<\/jats:p>","DOI":"10.3390\/v15040893","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T03:02:01Z","timestamp":1680231721000},"page":"893","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Validation of HIV-1 MA Shell Structural Arrangements and Env Protein Interactions Predict a Role of the MA Shell in Viral Maturation"],"prefix":"10.3390","volume":"15","author":[{"given":"Tarana A.","family":"Mangukia","sequence":"first","affiliation":[{"name":"Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy Ramielle L.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijie","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik","family":"Cesarz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9145-8436","authenticated-orcid":false,"given":"Carlos D.","family":"Ort\u00edz Hidalgo","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Havana, Havana 10400, Cuba"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4048-4658","authenticated-orcid":false,"given":"Marcelo","family":"Marcet-Palacios","sequence":"additional","affiliation":[{"name":"Department of Medicine, Alberta Respiratory Centre, University of Alberta, Edmonton, AB T6G 2S2, Canada"},{"name":"Department of Biological Sciences Technology, Laboratory Research and Biotechnology, Northern Alberta Institute of Technology, Edmonton, AB T5G 2R1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.virol.2009.02.048","article-title":"HIV-1 matrix organizes as a hexamer of trimers on membranes containing phosphatidylinositol-(4,5)-bisphosphate","volume":"387","author":"Alfadhli","year":"2009","journal-title":"Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.tim.2015.09.003","article-title":"The HIV-1 Entry Process: A Stoichiometric View","volume":"23","author":"Brandenberg","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Brandenberg, O.F., Magnus, C., Rusert, P., Regoes, R.R., and Trkola, A. 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