Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.

Blood matters: the hematological signatures of Coronavirus infection / Toro, Ayelen; Arévalo, Ana P.; Pereira-Gómez, Marianoel; Sabater, Agustina; Zizzi, Eric A.; Perbolianachis, Paula; Pascual, Gaston; Lage-Vickers, Sofia; Pórfido, Jorge L.; Achinelli, Ines; Seniuk, Rocio; Bizzotto, Juan; Sanchis, Pablo; Olivera, Alvaro; Leyva, Alejandro; Moreno, Pilar; Costábile, Alicia; Fajardo, Alvaro; Carrión, Federico; Fló, Martín; Olivero-Deibe, Natalia; Rodriguez, Fernando; Nin, Nicolas; Anselmino, Nicolas; Labanca, Estefania; Vazquez, Elba; Cotignola, Javier; Alonso, Daniel F.; Valacco, Maria P.; Marti, Marcelo; Gentile, Francesco; Cherkasov, Artem; Crispo, Martina; Moratorio, Gonzalo; Gueron, Geraldine. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 15:11(2024). [10.1038/s41419-024-07247-8]

Blood matters: the hematological signatures of Coronavirus infection

Zizzi, Eric A.;Gentile, Francesco;
2024

Abstract

Recent developments have broadened our perception of SARS-CoV-2, indicating its capability to affect the body systemically beyond its initial recognition as a mere respiratory pathogen. However, the pathways of its widespread are not well understood. Employing a dual-modality approach, we integrated findings from a Murine Hepatitis Virus (MHV) infection model with corroborative clinical data to investigate the pervasive reach of Coronaviruses. The novel presence of viral particles within red blood cells (RBCs) was demonstrated via high-resolution transmission electron microscopy, with computational modeling elucidating a potential heme-mediated viral entry mechanism via Spike protein affinity. Our data affirm viral localization in RBCs, suggesting heme moieties as facilitators for cellular invasion. Exacerbation of MHV pathology upon hemin administration, contrasted with chloroquine-mediated amelioration, underscoring a heme-centric pathway in disease progression. These observations extend the paradigm of Coronavirus pathogenicity to include hemoprotein interactions. This study casts new light on the systemic invasion capabilities of Coronaviruses, linking RBC hemoproteins with viral virulence. The modulation of disease severity through heme-interacting agents heralds a promising avenue for COVID-19 therapeutics. Our findings propose a paradigm shift in the treatment approach, leveraging the virus-heme interplay as a strategic hinge for intervention.
File in questo prodotto:
File Dimensione Formato  
s41419-024-07247-8.pdf

accesso aperto

Descrizione: Published Article
Tipologia: 2a Post-print versione editoriale / Version of Record
Licenza: Creative commons
Dimensione 5.56 MB
Formato Adobe PDF
5.56 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11583/2995191