AbstractBackground: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences.
Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, and Dengue genomes identifies strong RBP binding sites in these viral genomes. Replication and expression of viral sequences is expected to increasingly sequester RBPs - SRSF1 and RNPS1. Ordinarily, RBPs bound to nascent host transcripts prevents their annealing to complementary DNA. Their depletion induces destabilizing R-loops. Chromosomal breakage occurs when an excess of unresolved R-loops collide with incoming replication forks, overwhelming the DNA repair machinery. We estimated stoichiometry of inhibition of RBPs in host nuclear RNA by counting competing binding sites in replicating viral genomes and host RNA
.Results: Host RBP binding sites are frequent and conserved among different strains of RNA viral genomes. Similar binding motifs of SRSF1 and RNPS1 explain why DNA damage resulting from SRSF1 depletion is complemented by expression of RNPS1. Clustering of strong RBP binding sites coincides with the distribution of RNA-DNA hybridization sites across the genome. SARS-CoV-2 replication is estimated to require 32.5-41.8 hours to effectively compete for binding of an equal proportion of SRSF1 binding sites in host encoded nuclear RNAs. Significant changes in expression of transcripts encoding DNA repair and apoptotic proteins were found in an analysis of influenza A and Dengue-infected cells in some individuals.
Conclusions: R-loop-induced apoptosis indirectly resulting from viral replication could release significant quantities of membrane-associated virions into neighboring alveoli. These could infect adjacent pneumocytes and other tissues, rapidly compromising lung function, causing multiorgan system failure and other described symptoms.
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Here is an intriguing COMPUTER MODEL -GENERATED PREPRINT of a proposed mechanism by which COVID and possibly the vaccine could be causing the apoptosis of the cell and the spilling out of the infection into the body
THRUST OF PROPOSAL: "We propose an alternative mechanism in which infection of RNA virus triggers unrepaired sites of chromosomal breakage, causing apoptosis and consequentially, high-titer viral release. This is precipitated by the binding of RNA binding proteins to viral genomes and transcripts instead of nuclear transcripts, to prevent destabilization of chromosome structure." -------------------------------------------------------------------------------------------
Thank you Doctor Rowen for sharing all this information with all of us in this newsletter. You are a True Hero!
I love the Glen Beck info. I am sad to hear him start out his report calling Anthony Fauci head of the NIH, when, according to my research he is Director of the NIAID. According to Wikipedia is one of 27 Institutes which make up the Nation Institute of Health. Although he seems to have done a lot of research, this lack of attention to this detail, which I remembered, leaves me leaves me wondering what other things he is being sloppy about. I would love to share this report of his with my intelligent friends: and I fear they will disregard him when he starts out his report with such an easily spotted faux pas. Sorry to nit pick. I makes me sad that skeptics might see that and say it looks like he doesn't know what he's talking about. If I was smarter, I would let him know. Thank You again for the miraculous work, that you and your charming wife are doing. My life is so much better since I met you.
SO SORRY! HERE IS THE ABSTRACT, PLUS A PDF IS AVAILABLE The video is wonderful.
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https://f1000research.com/articles/9-943/v2
A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections [version 2; peer review: 4 approved]
Peter K. Rogan https://orcid.org/0000-0003-2070-52541,2, Eliseos J. Mucaki1, Ben C. Shirley2Author details
AbstractBackground: Certain riboviruses can cause severe pulmonary complications leading to death in some infected patients. We propose that DNA damage induced-apoptosis accelerates viral release, triggered by depletion of host RNA binding proteins (RBPs) from nuclear RNA bound to replicating viral sequences.
Methods: Information theory-based analysis of interactions between RBPs and individual sequences in the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, and Dengue genomes identifies strong RBP binding sites in these viral genomes. Replication and expression of viral sequences is expected to increasingly sequester RBPs - SRSF1 and RNPS1. Ordinarily, RBPs bound to nascent host transcripts prevents their annealing to complementary DNA. Their depletion induces destabilizing R-loops. Chromosomal breakage occurs when an excess of unresolved R-loops collide with incoming replication forks, overwhelming the DNA repair machinery. We estimated stoichiometry of inhibition of RBPs in host nuclear RNA by counting competing binding sites in replicating viral genomes and host RNA
.Results: Host RBP binding sites are frequent and conserved among different strains of RNA viral genomes. Similar binding motifs of SRSF1 and RNPS1 explain why DNA damage resulting from SRSF1 depletion is complemented by expression of RNPS1. Clustering of strong RBP binding sites coincides with the distribution of RNA-DNA hybridization sites across the genome. SARS-CoV-2 replication is estimated to require 32.5-41.8 hours to effectively compete for binding of an equal proportion of SRSF1 binding sites in host encoded nuclear RNAs. Significant changes in expression of transcripts encoding DNA repair and apoptotic proteins were found in an analysis of influenza A and Dengue-infected cells in some individuals.
Conclusions: R-loop-induced apoptosis indirectly resulting from viral replication could release significant quantities of membrane-associated virions into neighboring alveoli. These could infect adjacent pneumocytes and other tissues, rapidly compromising lung function, causing multiorgan system failure and other described symptoms.
THANK YOU FOR SHARING YOUR ABSOLUTELY FANTASTIC ARTICLES!!!
Here is an intriguing COMPUTER MODEL -GENERATED PREPRINT of a proposed mechanism by which COVID and possibly the vaccine could be causing the apoptosis of the cell and the spilling out of the infection into the body
.HTTPS://F1000RESEARCH.COM/ARTICLES/9-943/V2RESEARCH ARTICLEREVISED A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections
THRUST OF PROPOSAL: "We propose an alternative mechanism in which infection of RNA virus triggers unrepaired sites of chromosomal breakage, causing apoptosis and consequentially, high-titer viral release. This is precipitated by the binding of RNA binding proteins to viral genomes and transcripts instead of nuclear transcripts, to prevent destabilization of chromosome structure." -------------------------------------------------------------------------------------------
Plus, here is a link to a video discussion of this preprint, computer generated hypothesis: https://www.youtube.com/watch?v=6jNo0on8vhg&t=486s
Thank you Doctor Rowen for sharing all this information with all of us in this newsletter. You are a True Hero!
I love the Glen Beck info. I am sad to hear him start out his report calling Anthony Fauci head of the NIH, when, according to my research he is Director of the NIAID. According to Wikipedia is one of 27 Institutes which make up the Nation Institute of Health. Although he seems to have done a lot of research, this lack of attention to this detail, which I remembered, leaves me leaves me wondering what other things he is being sloppy about. I would love to share this report of his with my intelligent friends: and I fear they will disregard him when he starts out his report with such an easily spotted faux pas. Sorry to nit pick. I makes me sad that skeptics might see that and say it looks like he doesn't know what he's talking about. If I was smarter, I would let him know. Thank You again for the miraculous work, that you and your charming wife are doing. My life is so much better since I met you.