Human endogenous retrovirus K in the respiratory tract is associated with COVID-19 physiopathology

Abstract

Background Critically ill 2019 coronavirus disease (COVID-19) patients under invasive mechanical ventilation (IMV) are 10 to 40 times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation, and coagulopathy, the mechanisms involved in the progression to severity are poorly understood. Methods The virome of tracheal aspirates (TA) from 25 COVID-19 patients under IMV was assessed through unbiased RNA sequencing (RNA-seq), and correlation analyses were conducted using available clinical data. Unbiased sequences from nasopharyngeal swabs (NS) from mild cases and TA from non-COVID patients were included in our study for further comparisons. Results We found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes in TA from critically ill and deceased patients when comparing nasopharyngeal swabs from mild cases to TA from non-COVID patients. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days of diagnosis) in the intensive care unit. Increased HERV-K expression in deceased patients was associated with IL-17-related inflammation, monocyte activation, and an increased consumption of clotting/fibrinolysis factors. Moreover, increased HERV-K expression was detected in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. Conclusion Our data implicate the levels of HERV-K transcripts in the physiopathology of COVID-19 in the respiratory tract of patients under invasive mechanical ventilation.

Unveiling HERV‐K113‐ENV as SARS‐CoV‐2 severity admissible biomarker by mining transcriptome data

“…On the other hand, 75.00% (9/12) of severe/moderate and 25.00% (3/12) of healthy/asymptomatic/mild COVID‐19 cases HERV‐K113‐ENV is transcriptionally inactive (Figure 1F,G ). Interestingly, the role of HERV‐K113 in SARS‐CoV‐2 cases in the Brazilian population has also been reported, 2 further our analysis of Brazilian transcriptomes revealed that 60% (15/25) diseased/discharged cases of HERV‐K113‐ENV seem to be transcriptionally inactive, but transcriptionally active in 80% (4/5) non‐COVID‐19 cases. Collectively, the risk of hospitalization for COVID‐19‐positive humans becoming a severe/moderate condition is largely eliminated until the HERV‐K113‐ENV component is actively transcribed.…”

Alterations in the respiratory tract microbiome in COVID-19: current observations and potential significance

“…In a small sample of critically ill patients, however, five of ten showed an increase in viral abundance, including viruses EBV, CMV, TTV, HSV, HPVB19, and JCV [ 86 ]. Additionally, an examination of the human endogenous retrovirus K found increased expression in endotracheal aspirate from intubated COVID-19 compared to intubated non-COVID-19 patients, but found no difference in outcome within COVID-19 [ 87 ]. Finally, Merenstein and colleagues found elevated levels of the commensal DNA virus Anelloviridae and recently described Redondoviridae in the oropharynx of intubated relative to non-intubated COVID-19 patients [ 64 ].…”

Transcriptional and reverse transcriptional regulation of host genes by human endogenous retroviruses in cancers

“…Most HERVs are silent in healthy adult cells and tissues, but proviral RNAs or proteins were observed in several diseases, such as inflammation, autoimmune diseases, and malignancies ( Grandi and Tramontano, 2018a ; Tokuyama et al, 2018 ; Licastro and Porcellini, 2021 ). Recently, several studies reported that HERV-K expression was increased after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection both in vivo and in vitro ( Guo et al, 2022 ; Temerozo et al, 2022 ). Interestingly, evidence showed that HERV activity correlated with cell proliferation.…”