{"doi":"10.1016/j.ebiom.2021.103363","title":"HERV-W envelope expression in blood leukocytes as a marker of disease severity of COVID-19","abstract":"We are currently in the midst of a pandemic, caused by SARS-CoV-2, that has shaken the entire social and economic fabric of society. Within less than a year it spread across the entire globe and has spared no country, society, race or age group. Even several world leaders have been infected. While we have made great progress towards developing effective vaccines, to date we do not have any effective anti-viral agents. This desperate situation has called for desperate measures. For example, hydroxychloroquine was initially used for treating the infection based on minimal in vitro data, resulting in world-wide shortages of the drug, only for subsequent clinical trials to show that it was ineffective in treating the infection. It has become clear however, that in the early phases of the infection particularly in hospitalized patients, anti-inflammatory measures such as the use of corticosteroids can be helpful. All the same, potent immunosuppression can be detrimental to the host since this is what is necessary for the ultimate recovery of the patient. Hence better methods are necessary that would modulate the immune system more precisely to prevent organ damage and yet preserve the antiviral effects. The current study by Balestrieri et al. in EBioMedicine, studied 30 hospitalized patients infected with SARS-CoV-2 with a wide range of severity of illnesses. They were classified as asymptomatic, presymptomatic, mild, moderate or severe. 24/30 patients were males. They determined the expression of the envelope protein of an endogenous retrovirus family W (HERV-W), in blood leukocytes and compared it to other immune markers and the clinical status of the individuals [[1]Balestrieri E. Minutolo A. Petrone V. et al.Evidence of the pathogenic HERV-W envelope expression in T lymphocytes in association with the respiratory outcome of COVID-19 patients.EBioMedicine. 2021; https://doi.org/10.1016/j.ebiom.2021.103341Summary Full Text Full Text PDF PubMed Scopus (40) Google Scholar]. The expression of HERV-W envelope protein has been previously implicated in certain autoimmune diseases, such as multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy and type 1 diabetes. Increased levels of HERV-W transcripts have also been found in schizophrenia and bipolar disorder [[2]Küry P. Nath A. Créange A. et al.Human endogenous retroviruses diseases.Trends Mol Med. 2018; 24: 379-394Summary Full Text Full Text PDF PubMed Scopus (165) Google Scholar]. HERVs are retroviral elements derived from retroviruses that infected the human ancestral genome millions of years ago and were incorporated into the chromosomal DNA. Over the years they have become highly mutated; however, several of these genes still have an open reading frame (ORF). Even though there are 22 complete HERV-W families in the human genome, an ORF for the envelope protein is only present in chromosome 7q21.2 [[3]Voisset C. Ceclie O. Bedin F. et al.Chromosomal distribution and coding capacity of the human endogenous retrovirus HERV-W family.AIDS Res and Hum Retrovir. 2000; 16: 731-740Crossref PubMed Scopus (92) Google Scholar,[4]Kim H.S. Kim D.S. Huh J.W. et al.Molecular characterization of the HERV-W env gene in humans and primates: expression, FISH, phylogeny, and evolution.Mol Cells. 2008; 26: 53-60PubMed Google Scholar]. The expression of this protein is tightly regulated. It is highly expressed in the human placenta in syncytiotrophoblasts where it is critical for syncytial formation. For this reason, the protein is also called syncytin [[5]Blond J.L. Lavillette D. Cheynet V. et al.An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor.J Virol. 2020; 74: 3321-3329Crossref Scopus (550) Google Scholar]. However, the protein is epigenetically silenced in the fetus and in adulthood. Reactivation of the gene following thymic development can result in an inflam","journal":"EBioMedicine","year":2021,"id":187821,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230801,"name":"Avindra Nath","orcid":"0000-0003-0927-5855","position":1,"is_corresponding":false},{"id":661479,"name":"Marta García‐Montojo","orcid":"0000-0003-0664-3480","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-18T23:48:55.420619Z","pmid":"33993053","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}