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10.1073/pnas.2112663119

http://scihub22266oqcxt.onion/10.1073/pnas.2112663119
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35064076!8833170!35064076
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suck abstract from ncbi


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pmid35064076      Proc+Natl+Acad+Sci+U+S+A 2022 ; 119 (6): ä
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  • Impact of ADAR-induced editing of minor viral RNA populations on replication and transmission of SARS-CoV-2 #MMPMID35064076
  • Ringlander J; Fingal J; Kann H; Prakash K; Rydell G; Andersson M; Martner A; Lindh M; Horal P; Hellstrand K; Kann M
  • Proc Natl Acad Sci U S A 2022[Feb]; 119 (6): ä PMID35064076show ga
  • Adenosine deaminases acting on RNA (ADAR) are RNA-editing enzymes that may restrict viral infection. We have utilized deep sequencing to determine adenosine to guanine (A-->G) mutations, signifying ADAR activity, in clinical samples retrieved from 93 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in the early phase of the COVID-19 pandemic. A-->G mutations were detected in 0.035% (median) of RNA residues and were predominantly nonsynonymous. These mutations were rarely detected in the major viral population but were abundant in minor viral populations in which A-->G was more prevalent than any other mutation (P < 0.001). The A-->G substitutions accumulated in the spike protein gene at positions corresponding to amino acids 505 to 510 in the receptor binding motif and at amino acids 650 to 655. The frequency of A-->G mutations in minor viral populations was significantly associated with low viral load (P < 0.001). We additionally analyzed A-->G mutations in 288,247 SARS-CoV-2 major (consensus) sequences representing the dominant viral population. The A-->G mutations observed in minor viral populations in the initial patient cohort were increasingly detected in European consensus sequences between March and June 2020 (P < 0.001) followed by a decline of these mutations in autumn and early winter (P < 0.001). We propose that ADAR-induced deamination of RNA is a significant source of mutated SARS-CoV-2 and hypothesize that the degree of RNA deamination may determine or reflect viral fitness and infectivity.
  • |*Point Mutation[MESH]
  • |*RNA Editing[MESH]
  • |Adenosine Deaminase/*genetics/metabolism[MESH]
  • |Adenosine/metabolism[MESH]
  • |Adult[MESH]
  • |Aged[MESH]
  • |Aged, 80 and over[MESH]
  • |Amino Acid Substitution[MESH]
  • |COVID-19/*epidemiology/genetics/transmission/virology[MESH]
  • |Deamination[MESH]
  • |Female[MESH]
  • |Genetic Fitness[MESH]
  • |Genome, Viral[MESH]
  • |Guanine/metabolism[MESH]
  • |Host-Pathogen Interactions/genetics[MESH]
  • |Humans[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |RNA, Viral/*genetics/metabolism[MESH]
  • |RNA-Binding Proteins/*genetics/metabolism[MESH]
  • |SARS-CoV-2/*genetics/growth & development/pathogenicity[MESH]
  • |Signal Transduction[MESH]
  • |Spike Glycoprotein, Coronavirus/*genetics/metabolism[MESH]
  • |Sweden/epidemiology[MESH]
  • |Viral Load[MESH]


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