SARS-CoV-2 induces human endogenous retrovirus type W envelope protein expression in blood lymphocytes and in tissues of COVID-19 patients

Abstract

Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

Human endogenous retroviruses and the inflammatory response: A vicious circle associated with health and illness

“…Research relating HERVs to COVID-19 is ongoing and until now, accumulated data indicate differential expression of some HERV families during the acute phase of the disease, generally associated with enhancement of inflammatory processes ( 136 , 137 ). It was initially described that the envelope genes from HERV-W and HERV-K were highly expressed in peripheral blood mononuclear cells (PBMC) from healthy individuals exposed to SARS-CoV-2 in vitro , but only the HERV-W-env protein was synthesized.…”

COVID-19 mRNA vaccines and pathological cell-cell fusion: an unintended consequence

“…FCS was reported to activate HERVs, primarily type W and K, triggering not only cell-cell fusion but also hyperinflammatory responses and dysfunctional proteostasis [114][115][116][117]. HERVs are viral fossils embedded in human DNA that can be "awakened" by the infection with exogenous viruses, cancer, or neuropsychiatric conditions [118][119][120].…”

“…Several studies demonstrated that SARS-CoV-2 can activate HERV-W, an ancestral gene that encodes for the physiological placental fusogen syncytin-1 responsible for the merger of trophoblasts during the early pregnancy [114,115]. This suggests that the reproductive post-vaccine events may be triggered by the FCS pathology.…”

Do Messenger RNA Vaccines Induce Pathological Syncytia?

“…FCS was reported to activate HERVs, primarily type W and K, triggering not only cell-cell fusion but also hyperinflammatory responses and dysfunctional proteostasis [112][113][114][115]. HERVs are viral fossils embedded in human DNA that can be "awakened" by the infection with exogenous viruses, cancer, or neuropsychiatric conditions [116][117][118].…”

“…Several studies demonstrated that SARS-CoV-2 can activate HERV-W, an ancestral gene that encodes for the physiological placental fusogen syncytin-1 responsible for the merger of trophoblasts during the early pregnancy [112,113]. This suggests that the reproductive post-vaccine events may be triggered by the FCS pathology.…”