Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients

Abstract

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.

COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

“…Presumably, the potential negative impacts of HERV on cell homeostasis have to be kept under control to avoid adverse side effects. Furthermore, we evaluated the HERV transcriptional profiles, not their encoded proteins, and the enhanced expression of the MSRV-env protein was detected in the peripheral leucocytes of SARS-CoV-2-infected adults, including patients with severe respiratory disorders [ 55 ].…”

“…In cultured cells, the expression of retroviral elements was significantly up-regulated upon infection with SARS-CoV-2 [ 53 , 54 ]. Despite the potential mutual interplays between TRIM28/SETDB1, HERVs, and SARS-CoV-2, no investigations have explored their activation in patients affected by COVID-19, but a recent report that has highlighted the higher expression of MSRV-env in adults [ 55 ].…”

High CD169 Monocyte/Lymphocyte Ratio Reflects Immunophenotype Disruption and Oxygen Need in COVID-19 Patients

“…The CD57 marker has been used to assess functional immunodeficiency in several diseases, suggesting that positive cells do not proliferate, despite the preserved ability to secrete cytokines after activation [ 34 ]. COVID-19 patients have increased numbers of CD8+ T cells expressing CD57, which is considered a key marker of senescence and is associated with both human aging and chronic infections; CD57 expression was also recently described as having an association with other endogenous markers [ 35 , 36 ]. We also found an association of CD169 RMFI with PD1 expression, a molecule crucial for the induction and maintenance of peripheral tolerance and T-cell stability and integrity.…”

Multiple Sclerosis and SARS-CoV-2: Has the Interplay Started?

“…Accordingly, ENV is strongly expressed in blood cells of COVID-19 patients but not in healthy donors, and its level correlates with inflammatory mediators (IL-6, IL-17, and CXCR1), and with markers of T-cell exhaustion (e.g., PD1). Being predictive of a severe prognosis, ENV expression could play a role in immune overactivation and contribute to acute and chronic COVID-19 complications ( 135 ). In this context, HERVs could act as endogenous modulators of SARS-CoV-2/host interaction, helping to explain the extreme inter-individual variability in COVID-19 manifestations ( 136 ).…”