Abstract:Objective: The goals of the research were to determine if a foamy effect on macrophages was due to human
endogenous retrovirus K102 (HERV-K102) replication, and to further address its potential significance in HIV-1
infection.Methods: An RT-PCR HERV-K HML-2 pol method was used to screen the unknown HERV, and isolated bands were
sent for sequencing. Confirmation of RNA expression was performed by a real time quantitative PCR (qPCR) pol ddCt
method. Rabbit antibodies to Env peptides were used to assess expressio… Show more
“…While genomic DNA contains little or no uracil, reverse transcribed DNA can contain significant amounts (Longo et al 1990). When HML-2 viral particles are treated with UNG it results in a significant decrease in viral load (Laderoute et al 2007; Dube et al 2014; Laderoute et al 2015).…”
Section: Hml-2 Silencing Activation and Potential For Replicationmentioning
The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered “junk DNA” and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.
“…While genomic DNA contains little or no uracil, reverse transcribed DNA can contain significant amounts (Longo et al 1990). When HML-2 viral particles are treated with UNG it results in a significant decrease in viral load (Laderoute et al 2007; Dube et al 2014; Laderoute et al 2015).…”
Section: Hml-2 Silencing Activation and Potential For Replicationmentioning
The human genome contains a large number of retroviral elements acquired over the process of evolution, some of which are specific to primates. However, as many of these are defective or silenced through epigenetic changes, they were historically considered “junk DNA” and their potential role in human physiology or pathological circumstances have been poorly studied. The most recently acquired, human endogenous retrovirus-K (HERV-K), has multiple copies in the human genome and some of them have complete open reading frames that are transcribed and translated, especially in early embryogenesis. Phylogenetically, HERV-K is considered a supergroup of viruses. One of the subtypes, termed HML-2, seems to be the most active and hence, it is the best studied. Aberrant expression of HML-2 in adult tissues has been associated with certain types of cancer and with neurodegenerative diseases. This review discusses the discovery of these viruses, their classification, structure, regulation and potential for replication, physiological roles, and their involvement in disease pathogenesis. Finally, it presents different therapeutic approaches being considered to target these viruses.
“… Fig. 5 Complete RNA sequence of the Gag protein of the virus HERV-K102 [36] . The green subsequence of length 14 (271–285) is present in the RNA sequence of the protein S of virus SARS-CoV-2 [22] .…”
Section: Resultsmentioning
confidence: 99%
“…When we combine the antibody power originated by the endogenous human retrovirus HERV-K102 envelop protein (whose part of its mRNA is shared by the SARS-CoV-2 protein S [36] ) with the putative inhibitory role of circRNAs capable to block the miRNA-like action of SARS-CoV-2, one could understand why certain carriers of SARS-CoV-2 are completely asymptomatic and therefore, by mimicking their defence mechanisms, consider a possible therapy against SARS-CoV-2. Indeed, if we look on the “sponge effect” of circRNAs against microRNAs [37] , [38] , [39] , one can consider a therapeutic effect erasing pathogenic actions of microRNAs.…”
(1) Background: RNA viruses and especially coronaviruses could act inside host cells not only by building their own proteins, but also by perturbing the cell metabolism. We show the possibility of miRNA-like inhibitions by the SARS-CoV-2 concerning for example the hemoglobin and type I interferons syntheses, hence highly perturbing oxygen distribution in vital organs and immune response as described by clinicians
;
(2) Hypothesis: We hypothesize that short RNA sequences (about 20 nucleotides in length) from the SARS-CoV-2 virus genome can inhibit the translation of human proteins involved in oxygen metabolism, olfactory perception and immune system. (3) Methods: We compare RNA subsequences of SARS-CoV-2 protein S and RNA-dependent RNA polymerase genes to mRNA sequences of beta-globin and type I interferons; (4) Results: RNA subsequences longer than eight nucleotides from SARS-CoV-2 genome could hybridize subsequences of the mRNA of beta-globin and of type I interferons; (5) Conclusions: Beyond viral protein production, COVID-19 might affect vital processes like host oxygen transport and immune response.
“…HERV-K studies were conducted at the Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) in Bethesda, Maryland. The methodology has not been previously published and is based on previous studies showing that HERV-K viral particles contain both DNA and RNA genomes (11,(32)(33)(34). Investigators who performed the laboratory analysis of HERV-K were blinded to the samples.…”
Background: Neuroinflammation and human endogenous retroviruses (HERV) are thought to have a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). Therapy directed against endogenous retroviruses has demonstrated positive effects during in vitro and biomarker studies. Consequently, the present study was undertaken to assess the safety and tolerability of long-term antiretroviral therapy (ART), Triumeq (abacavir, lamivudine, and dolutegravir) exposure in patients with ALS, and efficacy against biomarkers of disease progression. Methods: Patients were observed during a 10week lead-in period before receiving Triumeq treatment for 24 weeks at four specialist ALS centers. The primary outcomes were safety and tolerability. Secondary outcomes included HERV-K expression levels, urinary p75 ECD levels, neurophysiological parameters, and clinical indicators. The ENCALS prediction model was applied to provide an estimate of the cohort survival. The trial was registered (NCT02868580). Findings: 40 patients with ALS received Triumeq and 35 (88%) completed treatment. There were no drug-related serious adverse events; one patient was withdrawn from the study due to a drug-associated increase in liver enzymes. A favorable response on HERV-K expression levels was observed, accompanied by a decline in ALSFRS-R progression rate of 21.8% (95% CI À4.8%-48.6%) and the amount of urinary p75 ECD measured. One patient died five months after stopping treatment, while five were expected to have died during the treatment period (interquartile range 2-8). Interpretation: Long-term Triumeq exposure was safe and well tolerated in this cohort. There was suggestive indication for a possible biological response in some pharmacodynamic and clinical biomarkers. A larger international phase 3 trial will be deployed to assess the effect of Triumeq on overall survival and disease progression.
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