Abstract Summary/Description
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an ongoing threat to public health globally. The emergence of highly mutated variants displaying increased immune evasion and transmissibility have necessitated the need for updated vaccines, therapeutics, and diagnostic tools. The omicron subvariant JN.1 displays significant antigenic differences from previous omicron subvariants, owing to approximately 30 mutations within its spike protein. In June 2023, the FDA released recommendations for updated COVID-19 vaccines to be formulated against JN.1 instead of the previously dominant XBB.1.5 variant. Understanding viral infection in established models is crucial for expanding our knowledge of the basic virology of JN.1 and its subvariants, evaluating vaccine efficacy, and identifying key factors involved in host-virus interaction. In this study, Intranasal infection of K18-hACE2 mice with the SARS-CoV-2 Omicron subvariant JN.1 resulted in 100% survival. Weight loss and clinical disease indicators if present were mild and transient. Virus titers peaked in the lungs on day 3 before gradually declining on days 5, 6, and 7 after infection. JN.1 was found to productively infect nasal turbinate cells, with the highest viral RNA detected on day 5 post-infection. While low levels of viral RNA were detected in the brain tissue of infected mice, plaque assay revealed infectious virus was absent in all tissue homogenates. Our results indicate that intranasal infection with the SARS-CoV-2 Omicron subvariant JN.1 produces attenuated disease in K18-hACE2 mice, productive infection of respiratory tissues, and a marked decrease in neuroinvasion compared to previous variants.
