Scientists have used engineered mice to compare SARS-COV-2 Omicron subvariants and found that the BA.5 strain was more virulent likely due to its ability to rapidly replicate early during infection.
The research, published in the journal Science Advances, addresses a challenge to studying and understanding rapidly evolving variants of concern due to a lack of animal models for running tests that could help explain why variants and subvariants each behave differently in people.
The genetically modified mice, called K18-hACE2, used in the research express a human receptor that allowed SARS-COV-2 to enter otherwise inaccessible mouse cells.
“One of the things we found is that the strain that causes more pathology, BA.5, replicates much faster early on during infection,” said Avery August, a professor in the College of Veterinary Medicine (CVM) at Cornell University in the US.
“By doing that, the virus generates a really strong immune response, which then leads to increased pathology and symptoms compared to subvariants that don’t replicate as fast,” August said.
Prior to this study, there were no small animal models to study the new SARS-CoV-2 Omicron variants of concern, because no animals got sick with other variants, the researchers said.
“Our study allows us to use relatively older K18-hACE2 mice as a disease model to understand how the virus becomes pathogenic, and to test whether and how vaccines and antivirals work for the new Omicron sub-variants,” said Hector Aguilar-Carreno, a professor of virology at CVM.
Early Omicron BA.1 and BA.2 subvariants also replicated and spread in the K-18 mice, but they caused minimal illness and death.