SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients

Charvet, Benjamin; Brunel, Joanna; Pierquin, Justine; Iampietro, Mathieu; Décimo, Didier; Queruel, Nelly; Lucas, Alexandre; Encabo-Berzosa, María del Mar; Arenaz, Izaskun; Marmolejo, Tania Perez; Gonzalez, Arturo Ivan Gonzalez; Castorena-Maldonado, Armando; Mathieu, Cyrille; Küry, Patrick; Flores-Rivera, José; Torres-Ruiz, Fernanda; Ávila‐Ríos, Santiago; de, Gonzalo Salgado-Montes; Schoorlemmer, Jon; Perron, Hervé; Horvat, Branka

doi:10.1016/j.isci.2023.106604

Cited by 24 publications

(20 citation statements)

References 71 publications

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“…A comprehensive report including patients infected with different SARS-CoV-2 variants investigated different sites using a range of methods. Immunohistology analyses found that HERV-W ENV is expressed in postmortem tissues of lungs, gut, heart, brain parenchyma, and nasal mucosa from acute COVID-19 patients and the sites where HERV-W were found correlated to the clinical manifestations observed in the donor patients ( Charvet et al., 2023 ). Collectively, these findings indicate that HERV-W ENV serves not only as a COVID-19 severity biomarker but it may be functioning as an additional pathogenic factor influencing the severity of the disease.…”

Section: Exogenous Viruses and Hervsmentioning

confidence: 99%

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

da Silva,

Guedes,

Santos

et al. 2024

Front. Cell. Infect. Microbiol.

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The notion that viruses played a crucial role in the evolution of life is not a new concept. However, more recent insights suggest that this perception might be even more expansive, highlighting the ongoing impact of viruses on host evolution. Endogenous retroviruses (ERVs) are considered genomic remnants of ancient viral infections acquired throughout vertebrate evolution. Their exogenous counterparts once infected the host’s germline cells, eventually leading to the permanent endogenization of their respective proviruses. The success of ERV colonization is evident so that it constitutes 8% of the human genome. Emerging genomic studies indicate that endogenous retroviruses are not merely remnants of past infections but rather play a corollary role, despite not fully understood, in host genetic regulation. This review presents some evidence supporting the crucial role of endogenous retroviruses in regulating host genetics. We explore the involvement of human ERVs (HERVs) in key physiological processes, from their precise and orchestrated activities during cellular differentiation and pluripotency to their contributions to aging and cellular senescence. Additionally, we discuss the costs associated with hosting a substantial amount of preserved viral genetic material.

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Section: Exogenous Viruses and Hervsmentioning

confidence: 99%

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

da Silva,

Guedes,

Santos

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Interestingly, the higher expression levels of HERVs, including HERV‐K and HERV‐W, have been observed in COVID‐19 patients. It is suggested that they could be used as biomarker to predict COVID‐19 severity and disease outcome 20–22 …”

Section: Introductionmentioning

confidence: 99%

“…It is suggested that they could be used as biomarker to predict COVID-19 severity and disease outcome. [20][21][22] While many reports defined the activation of HERV-K in various cancers, research on the investigation of the HERV-K oncoprotein expression level in CC tissues is scarce. On the other side, the identification of various cofactors that accelerate HPV tumorigenesis into precancer lesions and CC will be supportive in the triage of patients in the clinical setting.…”

Section: Introductionmentioning

confidence: 99%

The expression analysis of human endogenous retrovirus‐K Env, Np9, and Rec transcripts in cervical cancer

Soleimani‐Jelodar,

Arashkia,

Shoja

et al. 2024

Journal of Medical Virology

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While infection with high‐risk human papillomavirus (HPV) types is necessary for cervical cancer (CC) development, it is not enough, and other risk factors are required. Several studies have reported the activation of HERV‐K in different cancers; however, the investigation of HERV‐K expression levels in CC is scarce. In this study, it was hypothesized that activation of HERV‐K could play an essential role in CC development. In this order, the expression levels of HERV‐K Env, Np9, and Rec transcripts were investigated on 147 normal to CC uterine cervical tissues using quantitative real‐time PCR. The significantly higher levels of HERV‐K Env and Np9 transcripts were found in patients with cervical intraepithelial neoplasia (CIN) II−III and CC groups compared to those in the normal/CIN I group. Expression of Rec transcript was also higher only in the CC group than normal/CIN I group. Among CC patients, meaningfully higher levels of HERV‐K Env and Np9 transcripts were found in patients with squamous cell carcinoma rather than in adenocarcinoma. When only the HPV 16 positive samples were investigated, it was found that the mean difference in Env and Np9 mRNA levels was meaningfully higher among precancer lesions and the cancer group in comparison with the normal group. However, the Rec mRNA level showed no significant differences. The association between the expression of HERV‐K genes was investigated, and a significant positive correlation of Env expression with Np9 transcript was found only in the group with precancer lesions (R = 0.6, p = 0.0037). Moreover, a significant positive correlation was found between Rec and Np9 transcripts in patients with normal cervix tissues (R = 0.26, p = 0.033). However, no correlations were observed between the expression of Env and Rec in the three groups. In conclusion, our results showed that HERV‐K transcripts, especially Env and Np9, upregulated during cervical lesion progression. These findings highlight the potential use of HERV‐K Env and Np9 as biomarkers for CC diagnosis and prognosis. Further investigation is needed to determine the clinical utility of these markers and whether targeting HERV‐K oncogenes could be a viable therapeutic strategy for CC.

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“…Accordingly, it was recently shown that SARS-CoV-2 directly activates the expression of the Human Endogenous Retrovirus-W envelope protein (HERV-W ENV) in lymphoid cells on the one hand and that such a process was found in microglia of post-mortem brains from COVID-19 in the absence of any viral stigma [ 10 ]. HERV-W ENV was also found to be highly expressed in leukocytes of COVID-19 patients, with a magnitude paralleling that of inflammation, disease severity and outcomes [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation

Tamouza,

Meyer,

Lucas

et al. 2023

Transl Psychiatry

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Epidemiology has repeatedly associated certain infections with a risk of further developing psychiatric diseases. Such infections can activate retro-transposable genetic elements (HERV) known to trigger immune receptors and impair synaptic plasticity of neuroreceptors. Since the HERV-W ENV protein was recently shown to co-cluster with pro-inflammatory cytokines in a subgroup of patients with schizophrenia or bipolar disorder, we questioned the influence of the COVID-19 pandemic on patients with psychosis spectrum disorders (PSD). Present results revealed that (i) SARS-CoV-2 serology shows high prevalence and titers of antibodies in PSD, (ii) HERV-W ENV is detected in seropositive individuals only and (iii) SARS-CoV-2 and HERV-W ENV positivity co-clustered with high serum levels of pro-inflammatory cytokines in psychotic patients. These results thus suggest that SARS-CoV-2 infection in many patients with psychotic disorders now admitted in the psychiatry department did not cause severe COVID-19. They also confirm the previously reported association of elevated serum pro-inflammatory cytokines and HERV-W ENV in a subgroup of psychotic patients. In the context of the COVID-19 pandemic, this cluster is only found in SARS-CoV-2 seropositive PSD cases, suggesting a dominant influence of this virus on HERV-W ENV and cytokine expression, and/or patients’ greater susceptibility to SARS-CoV-2 infection. Further investigation on an interplay between this viral infection and the clinical evolution of such PSD patients is needed. However, this repeatedly defined subgroup of psychotic patients with a pro-inflammatory phenotype and HERV expression calls for a differential therapeutic approach in psychoses, therefore for further precision medicine development.

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SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients

Cited by 24 publications

References 71 publications

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

Beyond pathogens: the intriguing genetic legacy of endogenous retroviruses in host physiology

The expression analysis of human endogenous retrovirus‐K Env, Np9, and Rec transcripts in cervical cancer

Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation

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