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Updated: Jun 17, 2026
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
Spatiotemporal Characterization of Changes in the Respiratory Tract and the Nervous System, Including the Eyes in
Malgorzata Rosiak1,2, Tom Schreiner1,2, Georg Beythien1,2
1Department of Pathology, University of Veterinary Medicine Hannover, 30159 Hannover, Germany.
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model's utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations.
Insights
This study tracked SARS-CoV-2 spread in K18-hACE2 mice, revealing viral antigen in the nose, brain, and lungs. The findings offer insights into COVID-19
Area of Science:
- Virology
- Pathology
- Neuroscience
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects multiple organ systems, including the nervous and ocular systems.
- Understanding extrapulmonary dissemination is crucial for managing COVID-19.
Purpose of the Study:
- To characterize the spatiotemporal distribution of SARS-CoV-2 antigen and pathology in K18-hACE2 mice.
- To investigate viral spread and associated lesions in the nose, lungs, brain, and eyes.
Main Methods:
- Retrospective analysis of intranasally SARS-CoV-2 infected K18-hACE2 mice.
- Histology, immunohistochemistry, and RT-qPCR were used to examine tissues at 3, 6, and 7/8 days post-infection.
- Analysis included nasal, lung, brain, and ocular tissues.
Main Results:
- Viral antigen was prominent in the nose, brain, and lungs, with peak viral RNA in lungs and brain at 7/8 dpi.
- Brain infection correlated with meningoencephalitis and altered neurofilament immunoreactivity.
- Ocular tissues showed viral antigen in retinal ganglion cells without lesions, alongside microglial activation.
Conclusions:
- The K18-hACE2 mouse model effectively recapitulates extrapulmonary SARS-CoV-2 pathogenesis.
- Findings enhance understanding of SARS-CoV-2 neurotropism and ocular involvement.
- This model aids in studying the complex dynamics of viral spread and host response.
