Proteomics of circulating extracellular vesicles reveals diverse clinical presentations of COVID-19 but fails to identify viral peptides

Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypot...

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Autores: Gualdrón-López, Melisa|||0000-0002-8202-6751, Ayllon-Hermida, Alberto|||0000-0002-9566-6934, Cortés Serra, Núria|||0000-0001-5396-3757, Resa-Infante, Patricia|||0000-0002-1727-592X, Bech-Serra, Joan-Josep|||0000-0003-3486-781X, Aparici-Herraiz, Iris|||0000-0002-6014-8221, Nicolau Fernández, Marc|||0000-0001-7211-796X, Erkizia, Itziar|||0000-0003-1244-8972, Gutierrez-Chamorro, Lucia, Marfil, Sílvia|||0000-0003-0139-5000, Pradenas, Edwards|||0000-0001-5162-8920, Ávila Nieto, Carlos, Cucurull, Bernat, Montaner-Tarbés, Sergio, Muelas, Magdalena, Sotil, Ruth, Ballana, Ester|||0000-0002-5215-7363, Urrea, Víctor|||0000-0002-2577-856X, Fraile, Lorenzo|||0000-0002-8980-5862, Montoya, Maria|||0000-0002-5703-7360, Vergara-Alert, Júlia|||0000-0001-7484-444X, Segalés Coma, Joaquim|||0000-0002-1539-7261, Carrillo, Jorge|||0000-0003-0221-5948, Izquierdo Useros, Nuria|||0000-0002-1039-1821, Blanco, Julià|||0000-0002-2225-0217, Fernandez-Becerra, Carmen|||0000-0001-5154-0013, De La Torre, Carolina, Pinazo, Maria-Jesus|||0000-0002-4237-1075, Martínez Picado, Francisco Javier|||0000-0002-4916-2129, Del Portillo, Hernando A.|||0000-0002-5278-3452
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:307308
Acceso en línea:https://ddd.uab.cat/record/307308
https://dx.doi.org/urn:doi:10.3389/fcimb.2024.1442743
Access Level:acceso abierto
Palabra clave:COVID-19 patients
SARS-CoV-2
Antibody response
Extracellular vesicles
Immunocapture (CD9)
Ganglioside-capture (CD169/Siglec-1)
Size-exclusion chromatography (SEC)
Proteomics profiling
Descripción
Sumario:Extracellular vesicles (EVs) released by virus-infected cells have the potential to encapsulate viral peptides, a characteristic that could facilitate vaccine development. Furthermore, plasma-derived EVs may elucidate pathological changes occurring in distal tissues during viral infections. We hypothesized that molecular characterization of EVs isolated from COVID-19 patients would reveal peptides suitable for vaccine development. Blood samples were collected from three cohorts: severe COVID-19 patients (G1), mild/asymptomatic cases (G2), and SARS-CoV-2-negative healthcare workers (G3). Samples were obtained at two time points: during the initial phase of the pandemic in early 2020 (m0) and eight months later (m8). Clinical data analysis revealed elevated inflammatory markers in G1. Notably, non-vaccinated individuals in G1 exhibited increased levels of neutralizing antibodies at m8, suggesting prolonged exposure to viral antigens. Proteomic profiling of EVs was performed using three distinct methods: immunocapture (targeting CD9), ganglioside-capture (utilizing Siglec-1) and size-exclusion chromatography (SEC). Contrary to our hypothesis, this analysis failed to identify viral peptides. These findings were subsequently validated through Western blot analysis targeting the RBD of the SARS-CoV-2 Spike protein's and comparative studies using samples from experimentally infected Syrian hamsters. Furthermore, analysis of the EV cargo revealed a diverse molecular profile, including components involved in the regulation of viral replication, systemic inflammation, antigen presentation, and stress responses. These findings underscore the potential significance of EVs in the pathogenesis and progression of COVID-19.

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