Recent research used engineered mice to check SARS-COV-2 omicron subvariants and located one among them – BA.5 – was more virulent likely on account of its ability to rapidly replicate early during infection.
The study addresses a challenge to studying and understanding rapidly evolving variants of concern on account of an absence of animal models for running tests that might help explain why variants and subvariants each behave in another way in people.
The genetically modified mice, called K18-hACE2 mice, utilized in the research express a human receptor that allowed SARS-COV-2 to enter otherwise inaccessible mouse cells.
The strain that causes more pathology, BA.5, replicates much faster early on during infection. By doing that, the virus generates a very strong immune response, which then results in increased pathology and symptoms in comparison with subvariants that do not replicate as fast.”
Avery August, professor of microbiology and immunology and co-corresponding writer
“Prior to this study, there have been no small animal models to review the brand new SARS-CoV-2 Omicron variants of concern, because no animals got sick with other variants,” said Hector Aguilar-Carreño, professor of virology and co-corresponding writer. “Our study allows us to make use of relatively older K18-hACE2 mice as a disease model to grasp how the virus becomes pathogenic, and to check whether and the way vaccines and antivirals work for the brand new Omicron sub-variants.”
Early omicron BA.1 and BA.2 subvariants also replicated and spread within the K-18 mice but caused minimal illness and death. Alternatively, BA.5-infected mice exhibited significant weight reduction, high pathology in lungs, high levels of inflammatory cells and cytokines, signaling proteins which are related to inflammation. While some 3-month old mice survived, all 5 to eight month-old BA.5-infected mice died.
The animal model makes it possible for researchers to start to tease apart components of the immune system that might be focused on or blocked to potentially lessen or eliminate disease. Some scientists consider that targeting cytokines with drugs could provide a possible treatment that tempers the immune response and lessens symptoms.
The researchers found many similarities between the mouse model and the way these subvariants behave in humans, with BA.5 being more virulent in each. One big difference was that the majority individuals who developed illness from BA.5 didn’t die, but in K-18 mice, the subvariant was particularly pathogenic and lethal.
The studies were done in a high containment biosafety level 3 facility.
The study was funded by the National Institutes of Health.
Source:
Journal reference:
Imbiakha, B., et al. (2023). Age-dependent acquisition of pathogenicity by SARS-CoV-2 Omicron BA.5. Science Advances. doi.org/10.1126/sciadv.adj1736.