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Parental Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Predominates Over Coinfected SARS-CoV-2 Delta,

Kyeongbin Baek1, Dongbum Kim2, Bo Min Kang1

  • 1Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Republic of Korea.

Journal of Medical Virology
|November 20, 2024
PubMed

Insights

Parental SARS-CoV-2 dominates during coinfection, driving the evolution of variants with improved host adaptation. SARS-CoV-2 Delta contributes to this adaptation without direct genetic recombination.

Area of Science:

  • Virology
  • Evolutionary Biology
  • Infectious Diseases

Background:

  • SARS-CoV-2 evolution, including recombination, poses challenges for public health control and treatment.
  • Coinfection with different SARS-CoV-2 strains is a potential driver of viral evolution, but experimental data are limited.

Purpose of the Study:

  • To investigate the emergence and characteristics of SARS-CoV-2 variants following coinfection with parental SARS-CoV-2 and the Delta variant.
  • To assess the role of a long-term replication mouse model in studying SARS-CoV-2 coinfection dynamics.

Main Methods:

  • Coinfection of Calu-3 cells and a Calu-3 cell-derived xenograft mouse model with parental SARS-CoV-2 and SARS-CoV-2 Delta.
  • Serial passaging in cell culture and in vivo tumor models.
  • Analysis of viral mutations, plaque formation, cytopathic effects, and phylogenetic relationships.
  • Assessment of viral lethality through challenge studies.

Main Results:

  • Fewer mutations accumulated in cell passaging compared to the mouse model.
  • Tumor isolates exhibited diverse mutations and high-frequency simultaneous mutations, with no observed cytopathic effects or small plaque formation.
  • Phylogenetic analysis indicated variants retained the genetic makeup of parental SARS-CoV-2, not the Delta variant.
  • Viral isolates were less lethal than parental and Delta strains.

Conclusions:

  • Parental SARS-CoV-2 predominates over the Delta variant during coinfection.
  • SARS-CoV-2 Delta facilitates the evolution of parental SARS-CoV-2 variants towards enhanced host adaptation without recombination.
  • The mouse xenograft model is valuable for studying SARS-CoV-2 evolution during coinfection.
Keywords:
SARS‐CoV‐2coinfectionhost adaptationlong‐term infectionvirus mutants

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