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Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates
Xiao-Li Feng1, Dandan Yu2, Mi Zhang3
1Kunming National High-level Biosafety Research Center for Non-Human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650107, China.
Abstract:
The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally, from B.1.17 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) to B.1.1.529 (Omicron). The emerging or re-emerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics, pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2 (hACE2) transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.
Insights
The Alpha and Delta SARS-CoV-2 variants show more efficient replication in specific human cells and cause significant lung pathology in animal models. Continuous monitoring of these concerning variants remains crucial for public health.
Area of Science:
- Virology
- Pathogen Evolution
- Public Health
Background:
- The emergence of SARS-CoV-2 variants, including Alpha and Delta, poses a significant global health threat.
- Constant monitoring of variant epidemics, pathogenicity, and immune escape is essential.
Purpose of the Study:
- To characterize the replication and pathogenicity of Alpha and Delta SARS-CoV-2 variants isolated in Laos.
- To identify amino acid mutations in the spike protein of these variants.
Main Methods:
- Sequencing to determine amino acid mutations in the spike protein.
- In vitro cell culture experiments using Calu-3, Caco-2, Huh-7, Vero E6, and HPA-3 cells.
- In vivo animal studies using hACE2 transgenic mice and hamsters.
Main Results:
- Alpha and Delta isolates demonstrated more efficient replication than the prototype SARS-CoV-2 in Calu-3 and Caco-2 cells.
- Replication efficiency was not observed in Huh-7, Vero E6, and HPA-3 cells.
- Alpha and Delta variants replicated in multiple organs and induced moderate to severe lung pathology in animal models.
Conclusions:
- The spike protein mutations of isolated Alpha and Delta variants were characterized.
- The study evaluated the replication and pathogenicity of these SARS-CoV-2 variants in cellular and animal models.
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