Spike Proteins and Spike mRNA's translocate into the Nucleus. Reverse Transcriptase there Encodes Spike to Nuclear DNA. 2022-12-24. Jorma Jyrkkanen

Nuclear translocation of spike mRNA and protein is a novel pathogenic feature of SARS-CoV-2 Sarah Sattar,1,# Juraj Kabat,2,# Kailey Jerome,1 Friederike Feldmann,3 Kristina Bailey,4 and Masfique Mehedi1,#* Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe pathophysiology in vulnerable older populations and appears to be highly pathogenic and more transmissible than SARS-CoV or MERS-CoV [1, 2]. The spike (S) protein appears to be a major pathogenic factor that contributes to the unique pathogenesis of SARS-CoV-2. Although the S protein is a surface transmembrane type 1 glycoprotein, it has been predicted to be translocated into the nucleus due to the novel nuclear localization signal (NLS) “PRRARSV”, which is absent from the S protein of other coronaviruses. Indeed, S proteins translocate into the nucleus in SARS-CoV-2-infected cells. To our surprise, S mRNAs also translocate into the nucleus. S mRNA colocalizes with S protein, aiding the nuclear translocation of S mRNA. While nuclear translocation of nucleoprotein (N) has been shown in many coronaviruses, the nuclear translocation of both S mRNA and S protein reveals a novel pathogenic feature of SARS-CoV-2.

SARS-CoV-2 RNA reverse-transcribed and integrated into the human genome Liguo Zhang, Alexsia Richards, Andrew Khalil, Emile Wogram, Haiting Ma, Richard A. Young, Rudolf Jaenisch doi: https://doi.org/10.1101/2020.12.12.422516 This article is a preprint and has not been certified by peer review [what does this mean?]. 560105307787 Summary.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-infectious1–14. 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.

ALL OF THIS RAISES TWO INTERESTING QUESTIONS. 1. Does the encoded DNA spike fragment code then make the nuclear DNA a target for the immune system ie does it act as an antigen for autoimmune disease. 2. Does the rupture of mitochondria lead to failure of mitochondrial support for the immune system? The answer to 2 must be yes. The answere to 1 is being investigated as I write and it has been found to encode to liver nuclear DNA. Interestingly infants during the main pandemic had no respiratory epidemic but infants of vaccinated moms born after do and there is now an epidemic of infants with RSV-Flu-Covid suggesting in utero development of immune system damage (possibly epigenetically)which may have been caused by parental vaccination.