A proposed molecular mechanism for pathogenesis of severe RNA-viral pulmonary infections

Background: 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 bound replicating sequences. Methods: Information theory-based analysis interactions between RBPs and individual sequences the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), Influenza A (H3N2), HIV-1, Dengue genomes identifies strong RBP sites these genomes. Replication expression is expected increasingly sequester - SRSF1 RNPS1. Ordinarily, nascent transcripts prevents their annealing complementary DNA. Their induces destabilizing R-loops. Chromosomal breakage occurs when an excess unresolved R-loops collide with incoming replication forks, overwhelming repair machinery. estimated stoichiometry inhibition counting competing RNA. Results: Host are frequent conserved among different strains Similar motifs RNPS1 explain why resulting complemented Clustering coincides distribution RNA-DNA hybridization across genome. SARS-CoV-2 require 32.5-41.8 hours effectively compete for equal proportion encoded RNAs. Significant changes encoding apoptotic were found influenza Dengue-infected cells individuals. Conclusions: R-loop-induced apoptosis indirectly could release significant quantities membrane-associated virions into neighboring alveoli. These infect adjacent pneumocytes other tissues, rapidly compromising lung function, causing multiorgan system failure described symptoms.