tetano
Editor, Senior Moderator
J Med Virol
. 2024 Nov;96(11):e70072.
doi: 10.1002/jmv.70072. Parental Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Predominates Over Coinfected SARS-CoV-2 Delta, Producing Less Lethal Variants in a Long-Term Replication Mouse Model
Kyeongbin Baek[SUP] 1 [/SUP], Dongbum Kim[SUP] 2 [/SUP], Bo Min Kang[SUP] 1 [/SUP], Jinsoo Kim[SUP] 2 [/SUP], Atanas V Demirev[SUP] 3 [/SUP], Sangyi Lee[SUP] 3 [/SUP], Minyoung Kim[SUP] 1 [/SUP], Suyeon Kim[SUP] 1 [/SUP], Sangkyu Park[SUP] 4 [/SUP], Jin Il Kim[SUP] 3 [/SUP], Man-Seong Park[SUP] 3 [/SUP], Younghee Lee[SUP] 4 [/SUP], Hyung-Joo Kwon[SUP] 1 2 [/SUP]
Affiliations
The evolution of SARS-CoV-2, which limits public control and treatment, seems to have occurred through multiple mechanisms, including recombination of cocirculating strains in hosts. However, insufficient experimental data have been obtained after coinfection. Therefore, we investigated the emergence of variants after coinfection with parental SARS-CoV-2 and the SARS-CoV-2 Delta. We found that fewer (approximately 50%) mutations accumulated in Calu-3 cells than in other cells after serial passaging. Previously, we established a long-term replication mouse model by infecting Calu-3 cell-derived xenograft tumors with SARS-CoV-2. Here, we utilized our model to investigate the outcome after coinfection. More diverse viral mutations, along with multiple high-frequency simultaneous mutations, were discovered in the tumors than during cell passaging. Viral isolates from the tumors showed no cytopathic effects and formed much smaller plaques. Phylogenetic analysis suggested that the genetic makeup of the variants remained largely the same as that of parental SARS-CoV-2 rather than the SARS-CoV-2 Delta. Viral challenge revealed that the isolates were less lethal than the parental SARS-CoV-2 and SARS-CoV-2 Delta strains. These findings suggest that parental SARS-CoV-2 predominates over the SARS-CoV-2 Delta when coinfected, but the SARS-CoV-2 Delta contributes to the evolution of parental SARS-CoV-2 variants toward better host adaptation without recombination.
Keywords: SARS‐CoV‐2; coinfection; host adaptation; long‐term infection; virus mutants.
. 2024 Nov;96(11):e70072.
doi: 10.1002/jmv.70072. Parental Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Predominates Over Coinfected SARS-CoV-2 Delta, Producing Less Lethal Variants in a Long-Term Replication Mouse Model
Kyeongbin Baek[SUP] 1 [/SUP], Dongbum Kim[SUP] 2 [/SUP], Bo Min Kang[SUP] 1 [/SUP], Jinsoo Kim[SUP] 2 [/SUP], Atanas V Demirev[SUP] 3 [/SUP], Sangyi Lee[SUP] 3 [/SUP], Minyoung Kim[SUP] 1 [/SUP], Suyeon Kim[SUP] 1 [/SUP], Sangkyu Park[SUP] 4 [/SUP], Jin Il Kim[SUP] 3 [/SUP], Man-Seong Park[SUP] 3 [/SUP], Younghee Lee[SUP] 4 [/SUP], Hyung-Joo Kwon[SUP] 1 2 [/SUP]
Affiliations
- PMID: 39564900
- DOI: 10.1002/jmv.70072
The evolution of SARS-CoV-2, which limits public control and treatment, seems to have occurred through multiple mechanisms, including recombination of cocirculating strains in hosts. However, insufficient experimental data have been obtained after coinfection. Therefore, we investigated the emergence of variants after coinfection with parental SARS-CoV-2 and the SARS-CoV-2 Delta. We found that fewer (approximately 50%) mutations accumulated in Calu-3 cells than in other cells after serial passaging. Previously, we established a long-term replication mouse model by infecting Calu-3 cell-derived xenograft tumors with SARS-CoV-2. Here, we utilized our model to investigate the outcome after coinfection. More diverse viral mutations, along with multiple high-frequency simultaneous mutations, were discovered in the tumors than during cell passaging. Viral isolates from the tumors showed no cytopathic effects and formed much smaller plaques. Phylogenetic analysis suggested that the genetic makeup of the variants remained largely the same as that of parental SARS-CoV-2 rather than the SARS-CoV-2 Delta. Viral challenge revealed that the isolates were less lethal than the parental SARS-CoV-2 and SARS-CoV-2 Delta strains. These findings suggest that parental SARS-CoV-2 predominates over the SARS-CoV-2 Delta when coinfected, but the SARS-CoV-2 Delta contributes to the evolution of parental SARS-CoV-2 variants toward better host adaptation without recombination.
Keywords: SARS‐CoV‐2; coinfection; host adaptation; long‐term infection; virus mutants.