SARS-CoV-2 infection induces Human Endogenous Retrovirus Type W (HERV-W) Envelope (ENV) Protein Expression triggering a variety of clinical conditions


A new international study involving researchers from various institutions in France, Spain, Germany, Mexico and Switzerland has alarmingly found that SARS-CoV-2 infection induces Human Endogenous Retrovirus Type W (HERV-W) Envelope (ENV) Protein Expression in blood lymphocytes and tissues and can trigger a variety of clinical conditions, some of which are associated with Long COVID.

In a simple language, we could say that the conditions arising COVID-19 disease could actually be due to two pathogens ie the SARS-CoV-2 coronavirus and the human endogenous retrovirus type W (HERV-W) envelope (ENV) protein which also acts as an antigen that triggers both the innate and adaptive immunity.

The human coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently associated with high morbidity and mortality, and hospitals worldwide are facing the increasing demand of patients requiring oxygen supply, ventilators, and intensive care.

Despite dominant respiratory tract tropism, both pulmonary and extra-pulmonary SARS-CoV-2-related forms have been recognized [[1]], which predominantly involve the impairment of immune functions [[2]].

Innate immune hyper-activation combined with adaptive immune dysregulation has been recognized to play a critical role in the progression of the disease and thus in the clinical outcome of COVID-19 patients [[3],[4]], suggesting the critical evolution driven by exacerbated innate immunity and associated inflammation and lymphopenia [[5],[6]].

The immunological involvement includes hyper-immune reactions such as the “cytokine storm” syndrome (mostly occurring in pulmonary forms), the pediatric multisystem inflammatory syndrome, and immune-mediated cutaneous or neurological diseases along with various autoimmune manifestations such as dysregulation of coagulation mechanisms [7, 8, 9, 10].

With the aim to identify new factors contributing to dysregulated inflammation in COVID-19, as well as targets for therapeutic intervention and patient management, we studied the human endogenous retrovirus family W (HERV-W) that encodes an immunopathogenic and neurotoxic envelope protein HERV-W ENV, which has been associated with human inflammatory and/or autoimmune diseases [[11],[12]].

HERVs are genetic elements resulting from ancestral infection of germ line cells mediated by exogenous retroviruses and constitute up to 8% of the human genome. In the general population, their co-opting in physiological functions[[13]] and inter-individual variations such as copy number variations, unfixed copies and polymorphisms have been demonstrated [[14]].

Activation of HERVs has been demonstrated in cancer, multiple sclerosis, type 1 diabetes and rheumatoid arthritis [[11],[12],[15]], which represent the underlying conditions frequently detected in patients developing severe forms of COVID-19. Recent studies have confirmed the involvement of HERVs in inflammatory and neurological diseases [[14],[16]].

Specifically, the immunopathogenic protein HERV-W ENV can be activated by exogenous viruses [[17],[18]] and induces proinflammatory responses through the toll-like receptor 4 pathway (TLR4) [[19],[20]].

Furthermore, a humanized monoclonal antibody targeting the HERV-W ENV protein has been proposed as an innovative therapeutic approach for multiple sclerosis [[21]].

The present study aimed to evaluate the expression of HERV-W ENV in the peripheral blood cells of COVID-19 patients, its correlation with clinical characteristics, and its potential relationship with predicting the outcome of the disease.


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