Hi Pierre,
I've taken some notes and links from some of the video lectures I've taken the time to watch (
Thread ).
I haven't had time to dig deeper and connect the dots yet, but I thought that instead of keeping them until then, they might be useful to you in some way.
"Endogenous retroviruses (ERVs) are genetic parasites of vertebrate genomes. They are the 'footprints' of ancestral retrovirus infections that have integrated their genome into the germline of a host and then been transmitted vertically from generation to generation. Following germline colonisation, these elements can evolve in different ways. Some VRE can proliferate in the DNA of their host, resulting in the formation of multicopy families and the invasion of the genome of entire populations. Other elements may progressively degenerate and lose their ability to multiply, remaining only as fossil sequences in the host genome. Finally, some VREs may be retained, wholly or partially, by positive selection pressure if they provide a benefit to their host in terms of evolutionary success. This evolutionary diversity has resulted in a wide variety of VRE repertoires in different vertebrate species."
DeepL.
https://www.jle.com/fr/revues/vir/e...des_retrovirus_endogenes_284793/article.phtml
Abstract
"Schizophrenia and bipolar disorder are neuropsychiatric disorders of unknown origin. It seems that these two disorders share some common etiopathogenic mechanisms including genetic, environmental and inflammatory ones. Reactivation of the human endogenous retrovirus type W (HERV-W) can be a shared element in the pathophysiology of schizophrenia and bipolar disorder, linked to immuno-genetic and environment risk factors. We will present studies that have highlighted the presence of HERV-W in schizophrenic and bipolar disorder patients. We will then describe a two-hit model which could explain the common pathophysiological mechanism of affective and non-affective psychosis. Identification of immuno-inflammatory mediated subgroup of schizophrenia and bipolar disorder associated to HERV-W reactivation might open the way for the development of diagnostic biomarker and more targeted treatments. These new tools pave the way towards personalized psychiatry for a better care of patients."
Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire | médecine/sciences
Abstract
"Mammalian genomes contain a heavy load of retroelements, which are mobile sequences requiring reverse transcription for their amplification. A significant proportion of these elements is of retroviral origin, with thousands of sequences resembling the integrated form of infectious retroviruses with two LTRs bordering internal regions homologous to the gag, pol, and env genes. These elements, named endogenous retroviruses (ERVs), are thought to be the remnants of ancestral germline infections by active retroviruses, which have thereafter been transmitted in a Mendelian manner. The sequencing of several mammalian genomes has allowed a comprehensive study of their ERVs. They can be grouped according to sequence homologies into 10-100 families per genome, each containing a few to several hundred elements. Strong similarities between ERVs and present-day retroviruses can be inferred from phylogenetic analyses performed on the pol or env genes, suggesting a common history. As a general rule, most ERVs are old and degenerated, with their open reading frames disrupted, but a few proviruses have retained intact genes and the corresponding proteins can thus be expressed. Some elements still contain gag and pol genes that drive the synthesis of viral particles, as well as envelope genes whose product can be incorporated on their cognate or heterologous viral particles. This presentation will review the general properties of endogenous retroviruses, in relation with their possible consequences on vaccine production."
Risks linked to endogenous retroviruses for vaccine production: a general overview - PubMed
Summary
Prolonged SARS-CoV-2 RNA shedding and recurrence of PCR-positive tests have been
widely reported in patients after recovery, yet these patients most commonly are non-infectious.
Here we investigated the possibility that SARS-CoV-2 RNAs can be reverse-transcribed and
integrated into the human genome and that transcription of the integrated sequences might
account for PCR-positive tests. In support of this hypothesis, we found chimeric transcripts
consisting of viral fused to cellular sequences in published data sets of SARS-CoV-2 infected
cultured cells and primary cells of patients, consistent with the transcription of viral sequences
integrated into the genome. To experimentally corroborate the possibility of viral retro-
integration, we describe evidence that SARS-CoV-2 RNAs can be reverse transcribed in human
cells by reverse transcriptase (RT) from LINE-1 elements or by HIV-1 RT, and that these DNA
sequences can be integrated into the cell genome and subsequently be transcribed. Human
endogenous LINE-1 expression was induced upon SARS-CoV-2 infection or by cytokine
exposure in cultured cells, suggesting a molecular mechanism for SARS-CoV-2 retro-integration
in patients. This novel feature of SARS-CoV-2 infection may explain why patients can continue
to produce viral RNA after recovery and suggests a new aspect of RNA virus replication.
https://www.biorxiv.org/content/biorxiv/early/2020/12/13/2020.12.12.422516.full.pdf
SUMMARY
Beljanski discovers transforming RNAs. Excreted by mutant strains of Escherichi a coli , they are capable of transforming wild-type bacteria of the same species: they acquire the distinctive characteristics of the mutants and in turn excrete the transforming RNA.
The transforming RNAs are small and exceptionally rich in purine bases (G and A). They are synthesised by the PNPase, independently of the DNA, and normally remain 'stuck' to it: they also exist, in this inactive state, in wild-type bacteria. Under special circumstances, they can detach from the DNA and become active; this is what happens in mutants under the influence of the antibiotic showdomycin.
These RNAs can also transform bacteria of a different species from the one from which they originate. When they are taken up by a plant-cancer-causing bacterium, Agrobacterium tumefaciens, stable transformed strains appear, some of which have lost their tumorigenic potential.
The transformed strains no longer contain any trace of the transforming RNA. The transforming RNA has therefore transferred hereditary information from one bacterial strain to another. For the first time in the history of biology, proof has been provided that an RNA can cause a stable and heritable genetic transformation.
DeepL.
LES ARN TRANSFORMANTS
"Over the past decade, a large body of work has highlighted an ever-increasing number of RNA molecules that, unlike mRNAs, are not directly involved in the of RNA molecules that, unlike mRNAs, are not directly involved in protein synthesis.
protein synthesis. In other words, these RNAs are devoid of genetic information capable of coding for proteins. They are referred to as non-coding RNAs (ncRNAs) whose repertoire complexity equals or exceeds that of mRNAs.
repertoire equals or exceeds that of mRNAs. Although the biological function of the vast majority of ncRNAs remains largely enigmatic, some of them function as regulators of the flow of genetic information by controlling the
genetic information flow by controlling chromatin structure, regulation of transcription, mRNA stability and stability of mRNAs and the production and activity of proteins.
MicroRNAs and C/D snoRNAs are among the best characterised ncRNAs to date. These small ncRNAs selectively interact with other RNAs via base pairing and modify their
modify their reactivities. MicroRNAs block the translation of target mRNAs, whereas snoRNAs C/D snoRNAs guide the formation of chemical modifications (addition of methyl groups) at specific
positions along the target RNAs. The research activity of our team concerns a subclass of microRNAs and C/D snoRNAs whose gene expression defies the classical laws of heredity. Indeed, although the genes of these small ncRNAs are present in two copies in each nucleus (one allele inherited from the father, the other from the mother), only one of the two copies is active, and this strictly according to its parental origin. For example, for a given gene it is always the copy of paternal origin that is active, whereas the copy of maternal origin, which may be genetically identical, is silenced. There is therefore a "cellular memory" capable of distinguishing the parental origin of the alleles but also of modifying their activity. Such epigenetic phenomena are grouped under the term parental genomic imprinting.
In this talk, I will summarise our understanding of the production and mode of action of these small atypical ncRNAs, including a description of work that aims to elucidate the
physiological function of many microRNAs through the study of a knock-out mouse model. Finally, I will Finally, I will discuss the hypothesis that deregulations in the expression of certain C/D snoRNAs snoRNAs contribute to the etiology of a rare human disease: Prader-Willi syndrome."
https://www.academie-sciences.fr/pdf/conf/seance_100215.pdf
CBI -
We are writing to express concern about the use of a recombinant adenovirus type-5 (Ad5) vector for a COVID-19 phase 1 vaccine study,and subsequent advanced trials. Over a decade ago, we completed the Step and Phambili phase 2b studies that evaluated an Ad5 vectored HIV-1 vaccine administered in three immunisations for efficacy against HIV-1 acquisition. Both international studies found an increased risk of HIV-1 acquisition among vaccinated men.
The Step trial found that men who were Ad5 seropositive and uncircumcised on entry into the trial were at elevated risk of HIV-1 acquisition during the first 18 months of follow-up.
The hazard ratios were particularly high among men who were uncircumcised and Ad5 seropositive, and who reported unprotected insertive anal sex with a partner who was HIV-1 seropositive or had unknown serostatus at baseline, suggesting the potential for increased risk of penile acquisition of HIV-1. Importantly for considering the potential use of Ad5 vectors for COVID-19 infection, a similar increased risk of HIV infection was also observed in heterosexual men who enrolled in the Phambili study.
This effect appeared to persist over time. Both studies involved an Ad5 construct that did not have the HIV-1 envelope. In another HIV study, done only in men who were Ad5 seronegative and circumcised, a DNA prime followed by an Ad5 vector were used, in which both constructs contained the HIV-1 envelope.No increased risk of HIV infection was noted. A consensus conference about Ad5 vectors held in 2013 and sponsored by the National Institutes of Health indicated the most probable explanation for these differences related to the potential counterbalancing effects of envelope immune responses in mitigating the effects of the Ad5 vector on HIV-1 acquisition.The conclusion of this consensus conference warned that non-HIV vaccine trials that used similar vectors in areas of high HIV prevalence could lead to an increased risk of HIV-1 acquisition in the vaccinated population. The increased risk of HIV-1 acquisition appeared to be limited to men; a similar increase in risk was not seen in women in the Phambili trial.
Several follow-up studies suggested the potential mechanism for this increased susceptibility to HIV infection among men. The vaccine was highly immunogenic in the induction of HIV-specific CD4 and CD8 T cells; however, there was no difference in the frequency of T-cell responses after vaccination in men who did and did not later become infected with HIV in the Step Study.These findings suggest that immune responses induced by the HIV-specific vaccine were not the mechanism of increased acquisition. Participants with high frequencies of preimmunisation Ad5-specific T cells were associated with a decreased magnitude of HIV-specific CD4 responses and recipients of the vaccine had a decreased breadth of HIV-specific CD8 responses,suggesting that pre-existing Ad5 immunity might dampen desired vaccine-induced responses. Additional exploratory studies suggest that Ad5 immune complexes activate the dendritic cell–T cell axis, which might enhance HIV-1 replication in CD4 T cells.
Additionally, Ad5-specific CD4 T cells could have an increased susceptibility to HIV infection.In a non-human primate challenge study, infecting rhesus macaques with Ad5 and then immunising them with a replication-incompetent Simian immunodeficiency virus (SIV) vaccine based on Ad5 increased the risk of SIV acquisition from low-dose SIV penile challenge.Furthermore, subclinical inflammation and alterations to epithelial barriers at the inner foreskin, including increased densities of CCR5-positive CD4 T cells could contribute to high rates of sexually transmitted infections, including HIV, in uncircumcised men.
On the basis of these findings, we are concerned that use of an Ad5 vector for immunisation against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could similarly increase the risk of HIV-1 acquisition among men who receive the vaccine. Both the HIV and COVID-19 pandemics disproportionately affect vulnerable populations globally. Roll-out of an effective SARS-CoV-2 vaccine globally could be given to populations at risk of HIV infection, which could potentially increase their risk of HIV-1 acquisition.
This important safety consideration should be thoroughly evaluated before further development of Ad5 vaccines for SARS-CoV-2, and informed consent documents of these potential risks should reflect the considerable literature on HIV-1 acquisition with Ad5 vectors.
DEFINE_ME
Abstract
Understanding the emergence of novel viruses requires an accurate and comprehensive annotation of their genomes.
Overlapping genes (OLGs) are common in viruses and have been associated with pandemics but are still widely overlooked. We identify and characterize
ORF3d, a novel OLG in SARS-CoV-2 that is also present in Guangxi pangolin-CoVs but not other closely related pangolin-CoVs or bat-CoVs. We then document evidence of
ORF3d translation, characterize its protein sequence, and conduct an evolutionary analysis at three levels: between taxa (21 members of
Severe acute respiratory syndrome-related coronavirus), between human hosts (3978 SARS-CoV-2 consensus sequences), and within human hosts (401 deeply sequenced SARS-CoV-2 samples).
ORF3d has been independently identified and shown to elicit a strong antibody response in COVID-19 patients. However, it has been misclassified as the unrelated gene
ORF3b, leading to confusion.
Our results liken
ORF3d to other accessory genes in emerging viruses and highlight the importance of OLGs.
https://elifesciences.org/articles/59633
Abstract
Compared to adults, children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly mild or asymptomatic infections, but the underlying immunological differences remain unclear. Here, we describe clinical features, virology, longitudinal cellular, and cytokine immune profile, SARS-CoV-2-specific serology and salivary antibody responses in a family of two parents with PCR-confirmed symptomatic SARS-CoV-2 infection and their three children, who tested repeatedly SARS-CoV-2 PCR negative. Cellular immune profiles and cytokine responses of all children are similar to their parents at all timepoints. All family members have salivary anti-SARS-CoV-2 antibodies detected, predominantly IgA, that coincide with symptom resolution in 3 of 4 symptomatic members. Plasma from both parents and one child have IgG antibody against the S1 protein and virus-neutralizing activity detected. Using a systems serology approach, we demonstrate higher levels of SARS-CoV-2-specific antibody features of these family members compared to healthy controls. These data indicate that children can mount an immune response to SARS-CoV-2 without virological confirmation of infection, raising the possibility that immunity in children can prevent the establishment of SARS-CoV-2 infection. Relying on routine virological and serological testing may not identify exposed children, with implications for epidemiological and clinical studies across the life-span.
https://www.nature.com/articles/s41467-020-19545-8
I will post a short summary of Professor Luc Montagnier's video lecture on DNA emitting frequency later.