Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

Kitsou, Konstantina; Κοτανίδου, Αναστασία; Paraskevis, Dimitrios; Karamitros, Timokratis; Katzourakis, Aris; Tedder, Richard S.; Hurst, Tara; Sapounas, Spyros; Kotsinas, Athanassios; Gorgoulis, Vassilis G.; Spoulou, Vana; Tsiodras, Sotirios; Λάγιου, Παγώνα; Magiorkinis, Gkikas

doi:10.1128/spectrum.01260-21

Cited by 37 publications

(47 citation statements)

References 45 publications

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“…Identification of primary mechanisms of the viral effect could become the basis for diagnostic methods aimed at early detection of the nervous system impairment, and for the development of methods of treating neurological consequences. As has been already mentioned, the cause of long-term neurological consequences of COVID-19 includes activation of REs influenced by the virus [30][31][32][33], and REs have a regulatory effect on specific genes in neurons. The SARS-CoV-2 integration into the human genome via reverse transcriptase and RE endonuclease is also important [36], and has also been observed in other positivestranded RNA viruses [37].…”

Section: Long-term Neurological Consequences Of Covid-19mentioning

confidence: 91%

“…The experiment conducted on human cell lines demonstrated that SARS-CoV-2 infection resulted in increased levels of 52 different HERV and 40 LINE1 REs [30]. The transcriptome of bronchoalveolar lavage and peripheral blood monocytes obtained from COVID-19 patients was also characterized by a significant increase in the level of HERV transcripts, compared with healthy individuals [31]. The study involving 17 COVID-19 patients demonstrated an enhanced expression of HERV-W REs, compared with the control group.…”

Section: Introductionmentioning

confidence: 93%

“…An activating effect of SARS-CoV-2 on REs [30][31][32][33] causes serious changes in brain functioning, which could persist for a long period after recovery. This is evidenced by the data of multiple original studies analyzed in the conducted meta-analyses.…”

Section: Long-term Neurological Consequences Of Covid-19mentioning

confidence: 99%

“…LINE1 RE activation, initiated by SARS-CoV-2, reduces endothelial cell proliferation and migration via regulating the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF) and Tie-2 (protein kinase receptor) [34]. Therefore, one of the mechanisms of endothelial dysfunction, caused by SARS-CoV-2, may be the activation of REs caused by the virus [30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

et al. 2022

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Retroelements play a key role in brain functioning in humans and other animals, since they represent dynamic regulatory elements controlling the expression of specific neuron types. The activity of retroelements in the brain is impaired under the influence of SARS-CoV-2, penetrating the blood-brain barrier. We propose a new concept, according to which the neurological complications of COVID-19 and their long-term effects are caused by modified expression of retroelements in neurons due to viral effect. This effect is implemented in several ways: a direct effect of the virus on the promoter regions of retroelement-encoding genes, virus interaction with miRNAs causing silencing of transposons, and an effect of the viral RNA on the products of retroelement transcription. Aging-related physiological activation of retroelements in the elderly is responsible for more severe course of COVID-19. The associations of multiple sclerosis, Parkinson’s disease, Guillain-Barré syndrome, acute disseminated encephalomyelitis with coronavirus lesions also indicate the role of retroelements in such complications, because retroelements are involved in the mechanisms of the development of these diseases. According to meta-analyses, COVID-19-caused neurological complications ranged 36.4-73%. The neuropsychiatric consequences of COVID-19 are observed in patients over a long period after recovery, and their prevalence may exceed those during the acute phase of the disease. Even 12 months after recovery, unmotivated fatigue, headache, mental disorders, and neurocognitive impairment were observed in 82%, 60%, 26.2-45%, and 16.2-46.8% of patients, correspondingly. These manifestations are explained by the role of retroelements in the integration of SARS-CoV-2 into the human genome using their reverse transcriptase and endonuclease, which results in a long-term viral persistence. The research on the role of specific retroelements in these changes can become the basis for developing targeted therapy for neurological consequences of COVID-19 using miRNAs, since epigenetic changes in the functioning of the genome in neurons, affected by transposons, are reversible.

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Section: Long-term Neurological Consequences Of Covid-19mentioning

confidence: 91%

Section: Introductionmentioning

confidence: 93%

Section: Long-term Neurological Consequences Of Covid-19mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

et al. 2022

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“…As the main functional genes, HERV-K gag , env and pol gene encode matrix protein, envelope and polymerase, respectively [ 27 ]. High expression of HERVs was also found in the lavage fluid of COVID-19 patients [ 28 ], but the activation of HERV-K in patients with different clinical types was not reported. In view of the above phenomena, we suspected that HERV-K (HML-2) has an important ability to activate interferon, thus we explored whether the activation of interferon in moderate COVID-19 patients and severe COVID-19 patients is related to HERV-K (HML-2).…”

Section: Introductionmentioning

confidence: 99%

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Guo

Yang

Liu

et al. 2022

Viruses

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Background. Interferon is a marker of host antiviral immunity, which is disordered in COVID-19 patients. ERV can affect the secretion of interferon through the cGAS-STING pathway. In this study, we explored whether IFN-I and HERV-K (HML-2) were activated in COVID-19 patients and whether there was an interaction between them. Methods. We collected blood samples from COVID-19 patients and healthy controls. We first detected the expression of HERV-K (HML-2) gag, env, and pol genes and IFN-I-related genes between patients and healthy people by qPCR, synchronously detected VERO cells infected with SARS-CoV-2. Then, the chromosome distributions of highly expressed HERV-K (HML-2) gag, env, and pol genes were mapped by the next-generation sequencing results, and GO analysis was performed on the related genes. Results. We found that the HERV-K (HML-2) gag, env, and pol genes were highly expressed in COVID-19 patients and VERO cells infected with SARS-CoV-2. The interferon-related genes IFNB1, ISG15, and IFIT1 were also activated in COVID-19 patients, and GO analysis showed that HERV-K (HML-2) can regulate the secretion of interferon. Conclusions. The high expression of HERV-K (HML-2) might activate the increase of interferon in COVID-19 patients, proving that HERV-K does not only play a negative role in the human body.

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Human endogenous retroviruses in viral disease and therapy

Fan

Cui

2022

Clinical and Translational Dis

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As retained sequences of ancient retroviruses, human endogenous retroviruses (HERVs) are widespread in the human genome. Although most HERVs have been inert throughout evolution, several HERVs are still functional and involved in various diseases, such as autoimmune diseases, cancer, neurological diseases and viral infection. Hence, certain types of therapies targeting HERVs or utilizing HERV tools have been developed. Here, we summarize recent findings on the role of HERVs in viral infection, including HERV dysregulation in different kinds of viral infections and the potential mechanisms of HERV‐mediated antiviral immunity. In addition, we provide an overview of HERV‐related therapies that directly target HERVs or are indirectly based on HERVs to improve the efficacy of vaccines and drugs.

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Upregulation of Human Endogenous Retroviruses in Bronchoalveolar Lavage Fluid of COVID-19 Patients

Abstract: SARS-CoV-2 emerged in late 2019 in China, causing a global pandemic. Severe COVID-19 is characterized by intensive inflammatory responses, and older age is an important risk factor for unfavorable outcomes.

Cited by 37 publications

References 45 publications

Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

Role Of Retroelements In The Development Of COVID-19 Neurological Consequences

High Expression of HERV-K (HML-2) Might Stimulate Interferon in COVID-19 Patients

Human endogenous retroviruses in viral disease and therapy

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