Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients
Emanuela Balestrieri,
Antonella Minutolo,
Vita Petrone,
Marialaura Fanelli,
Marco Iannetta,
Vincenzo Malagnino,
Marta Zordan,
Pietro Vitale,
Benjamin Charvet,
Branka Horvat,
Sergio Bernardini,
Enrico Garaci,
Paolo di Francesco,
Paola Sinibaldi Vallebona,
Loredana Sarmati,
Sandro Grelli,
Massimo Andreoni,
Hervé Perron,
Claudia Matteucci
Affiliations
Emanuela Balestrieri
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Antonella Minutolo
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Vita Petrone
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Marialaura Fanelli
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Marco Iannetta
Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Vincenzo Malagnino
Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Marta Zordan
Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Pietro Vitale
Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Benjamin Charvet
International Center for Infectiology Research (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France; Geneuro – Innovation, Lyon 69008, France
Branka Horvat
International Center for Infectiology Research (CIRI), INSERM U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, University of Lyon, Lyon, France
Sergio Bernardini
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Enrico Garaci
IRCCS San Raffaele Pisana, Rome 00163, Italy
Paolo di Francesco
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy
Paola Sinibaldi Vallebona
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Institute of Translational Pharmacology, National Research Council, Rome 00133, Italy
Loredana Sarmati
Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Sandro Grelli
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Virology Unit, Policlinic of Tor Vergata, Rome 00133, Italy
Massimo Andreoni
Department of Systems Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Infectious Diseases Clinic, Policlinic of Tor Vergata, Rome 00133, Italy
Hervé Perron
Geneuro – Innovation, Lyon 69008, France; University of Lyon, Lyon 69007, France
Claudia Matteucci
Department of Experimental Medicine, University of Rome Tor Vergata, Rome 00133, Italy; Corresponding author.
Background: Despite an impressive effort in clinical research, no standard therapeutic approach for coronavirus disease 2019 (COVID-19) patients has been established, highlighting the need to identify early biomarkers for predicting disease progression and new therapeutic interventions for patient management. The present study aimed to evaluate the involvement of the human endogenous retrovirus -W envelope (HERV-W ENV) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection considering recent findings that HERVs are activated in response to infectious agents and lead to various immunopathological effects. We analysed HERV-W ENV expression in blood cells of COVID-19 patients in correlation with clinical characteristics and have discussed its potential role in the outcome of the disease. Methods: We analysed HERV-W ENV expression in blood samples of COVID-19 patients and healthy donors by flow cytometry and quantitative reverse transcriptase PCR analysis, and evaluated its correlation with clinical signs, inflammatory markers, cytokine expression, and disease progression. Findings: HERV-W ENV was highly expressed in the leukocytes of COVID-19 patients but not in those of healthy donors. Its expression correlated with the markers of T-cell differentiation and exhaustion and blood cytokine levels. The percentage of HERV-W ENV-positive lymphocytes correlated with inflammatory markers and pneumonia severity in COVID-19 patients. Notably, HERV-W ENV expression reflects the respiratory outcome of patients during hospitalization. Interpretation: Given the known immuno- and neuro-pathogenicity of HERV-W ENV protein, it could promote certain pathogenic features of COVID-19 and therefore serve as a biomarker to predict clinical progression of disease and open to further studies for therapeutic intervention. Funding: Information available at the end of the manuscript.
