2026-06-01T02:17:47Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/381722026-02-03T11:17:16Zcom_10630_2254col_10630_37953

Cross-Linking Mass Spectrometry Uncovers Interactions Between High-Density Lipoproteins and the SARS-CoV-2 Spike Glycoprotein. Burnap, Sean A. Ortega-Prieto, Ana María Jimenez-Guardeño, Jose Manuel Ali, Hashim Takov, Kaloyan Fish, Matthew Shankar-Hari, Manu Giacca, Mauro Malim, Michael H. Mayr, Manuel COVID-19 - Aspectos moleculares Virología High-density lipoprotein (HDL) levels are reduced in patients with coronavirus disease 2019 (COVID-19), and the extent of this reduction is associated with poor clinical outcomes. While lipoproteins are known to play a key role during the life cycle of the hepatitis C virus, their influence on coronavirus (CoV) infections is poorly understood. In this study, we utilize cross-linking mass spectrometry (XL-MS) to determine circulating protein interactors of the severe acute respiratory syndrome (SARS)-CoV-2 spike glycoprotein. XL-MS of plasma isolated from patients with COVID-19 uncovered HDL protein interaction networks, dominated by acute-phase serum amyloid proteins, whereby serum amyloid A2 was shown to bind to apolipoprotein (Apo) D. XL-MS on isolated HDL confirmed ApoD to interact with SARS-CoV-2 spike but not SARS-CoV-1 spike. Other direct interactions of SARS-CoV-2 spike upon HDL included ApoA1 and ApoC3. The interaction between ApoD and spike was further validated in cells using immunoprecipitation-MS, which uncovered a novel interaction between both ApoD and spike with membrane-associated progesterone receptor component 1. Mechanistically, XL-MS coupled with data-driven structural modeling determined that ApoD may interact within the receptor-binding domain of the spike. However, ApoD overexpression in multiple cell-based assays had no effect upon viral replication or infectivity. Thus, SARS-CoV-2 spike can bind to apolipoproteins on HDL, but these interactions do not appear to alter infectivity. 2025-03-20T07:47:31Z 2025-03-20T07:47:31Z 2025-03-20T07:47:31Z 2023 journal article https://hdl.handle.net/10630/38172 10.1016/j.mcpro.2023.100600 eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 Internacional Elsevier