tetano
Editor, Senior Moderator
Emerg Microbes Infect
. 2021 Aug 17;1-50.
doi: 10.1080/22221751.2021.1969868. Online ahead of print.
Host-dependent editing of SARS-CoV-2 in COVID-19 patients
Josep Gregori[SUP] 1 2 3 [/SUP], Maria Francesca Cortese[SUP] 4 [/SUP], Maria Piñana[SUP] 5 [/SUP], Carolina Campos[SUP] 1 2 [/SUP], Damir Garcia-Cehic[SUP] 1 2 [/SUP], Cristina Andrés[SUP] 5 [/SUP], Josep Francesc Abril[SUP] 6 [/SUP], Maria Gema Codina[SUP] 7 [/SUP], Ariadna Rando[SUP] 7 [/SUP], Juliana Esperalba[SUP] 7 [/SUP], Elena Sulleiro[SUP] 7 [/SUP], Joan Joseph[SUP] 7 [/SUP], Narcis Saubí[SUP] 7 [/SUP], Sergi Colomer-Castell[SUP] 1 [/SUP], Mari Carmen Martin[SUP] 5 [/SUP], Carla Castillo[SUP] 5 [/SUP], Juan Ignacio Esteban[SUP] 1 [/SUP], Tomas Pumarola[SUP] 7 8 [/SUP], Francisco Rodriguez-Frias[SUP] 2 4 8 [/SUP], Andrés Antón[SUP] 5 8 [/SUP], Josep Quer[SUP] 1 2 [/SUP]
Affiliations
Abstract
Introduction: A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables deep study of the viral quasispecies in samples from infected individuals.
Methods: In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease was investigated using next-generation sequencing (Illumina platform).
Results: SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations.
Conclusions: ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.
Keywords: ADAR1; SARS-CoV-2; editing; mutations; quasispecies.
. 2021 Aug 17;1-50.
doi: 10.1080/22221751.2021.1969868. Online ahead of print.
Host-dependent editing of SARS-CoV-2 in COVID-19 patients
Josep Gregori[SUP] 1 2 3 [/SUP], Maria Francesca Cortese[SUP] 4 [/SUP], Maria Piñana[SUP] 5 [/SUP], Carolina Campos[SUP] 1 2 [/SUP], Damir Garcia-Cehic[SUP] 1 2 [/SUP], Cristina Andrés[SUP] 5 [/SUP], Josep Francesc Abril[SUP] 6 [/SUP], Maria Gema Codina[SUP] 7 [/SUP], Ariadna Rando[SUP] 7 [/SUP], Juliana Esperalba[SUP] 7 [/SUP], Elena Sulleiro[SUP] 7 [/SUP], Joan Joseph[SUP] 7 [/SUP], Narcis Saubí[SUP] 7 [/SUP], Sergi Colomer-Castell[SUP] 1 [/SUP], Mari Carmen Martin[SUP] 5 [/SUP], Carla Castillo[SUP] 5 [/SUP], Juan Ignacio Esteban[SUP] 1 [/SUP], Tomas Pumarola[SUP] 7 8 [/SUP], Francisco Rodriguez-Frias[SUP] 2 4 8 [/SUP], Andrés Antón[SUP] 5 8 [/SUP], Josep Quer[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34402744
- DOI: 10.1080/22221751.2021.1969868
Abstract
Introduction: A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables deep study of the viral quasispecies in samples from infected individuals.
Methods: In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease was investigated using next-generation sequencing (Illumina platform).
Results: SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations.
Conclusions: ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.
Keywords: ADAR1; SARS-CoV-2; editing; mutations; quasispecies.