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J Med Virol . Deep Sequencing Reveals Dual Evolution of SARS-CoV-2: Insights Into Defective Genomes From Wuhan-Hu-1 Variants to Omicron Subvariants

tetano

Editor, Senior Moderator
J Med Virol


. 2025 Jul;97(7):e70476.
doi: 10.1002/jmv.70476. Deep Sequencing Reveals Dual Evolution of SARS-CoV-2: Insights Into Defective Genomes From Wuhan-Hu-1 Variants to Omicron Subvariants

Carolina Campos[SUP] 1 2 3 [/SUP], Marta Ibañez-Lligoña[SUP] 1 2 4 [/SUP], Sergi Colomer-Castell[SUP] 1 2 3 [/SUP], Josep Gregori[SUP] 1 2 [/SUP], Damir Garcia-Cehic[SUP] 1 2 5 [/SUP], Cristina Andrés[SUP] 6 7 [/SUP], Maria Piñana[SUP] 6 7 [/SUP], Alejandra González-Sánchez[SUP] 6 7 [/SUP], Ariadna Rando-Segura[SUP] 2 6 8 [/SUP], Juliana Esperalba[SUP] 6 8 [/SUP], Narcis Saubí[SUP] 6 8 [/SUP], Maria Francesca Cortese[SUP] 2 8 [/SUP], David Tabernero[SUP] 1 2 8 [/SUP], Francisco Rodriguez-Frias[SUP] 2 9 [/SUP], Roser Ferrer[SUP] 10 11 [/SUP], Juan Ignacio Esteban[SUP] 1 2 3 [/SUP], Renate W Kakze-van der Honing[SUP] 12 [/SUP], Andries A Kampfraath[SUP] 12 [/SUP], Júlia Vergara-Alert[SUP] 13 14 [/SUP], Joaquim Segalés[SUP] 13 15 [/SUP], Wim H M van der Poel[SUP] 12 [/SUP], Tomàs Pumarola[SUP] 6 7 16 [/SUP], Andrés Antón[SUP] 6 7 16 [/SUP], Josep Quer[SUP] 1 2 3 [/SUP]



Affiliations
Abstract

SARS-CoV-2 has evolved from early variants dominating the first (B.1.5, B.1.1) and second (B.1.177) pandemic waves, which exhibited a higher frequency of minority mutants with deletions leading to Defective Viral Genomes (DVGs) in the spike region near the S1/S2 cleavage site than the Alpha, Beta, and Delta variants. The emergence of Omicron has significantly altered the dominant variant profile, with Omicron subvariants now representing 100% of circulating viruses. To monitor the evolution and adaptation of Omicron in the human population, a deep-sequencing study was performed in RNA samples of BA.1, BA.1.1, BA.2, BA.5, BQ.1.1, XBB.1.5 and BA.2.86 Omicron subvariants. The findings reveal two occurrences of similar evolutionary patterns within SARS-CoV-2 characterized by a shift from a significant to a very low production of DVGs. This event suggests that DVGs might play a role in the virus's spread and adaptation for persistence in infected humans.

Keywords: DVGs; Omicron; deep‐sequencing; dual evolution; quasispecies.

 
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