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Updated: May 2, 2026
Viral Tracing of Genetically Defined Neural Circuitry
Published on: October 17, 2012
Mouse models of Tembusu virus infection for differentiating between cluster 2.1 and 2.2 isolates
Chonglun Feng1, Qiong Li1, Dongying Miao1
1National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, PR China.
Abstract:
Tembusu virus (TMUV) cluster 2.1 and 2.2 strains are known to produce lethal neurological disease in mice inoculated by intracerebral (ic) route. Here, we report the comparative clinicopathological findings following experimental infections of 3-week-old BALB/c and Kunming mice with cluster 2.1 isolate H and cluster 2.2 isolate Y. When infected by the subcutaneous (sc) route, both isolates failed to induce disease in mice. When infected by the ic route, both isolates caused lethal neurological disease in mice, with isolate H presenting markedly higher neurovirulence than isolate Y. Further studies with the Kunming mouse model showed that following sc inoculation, both H and Y isolates failed to replicate in brain and spleen, and that following ic inoculation, isolate H replicated to higher levels in brain and spleen than isolate Y. The findings may help to explain non-neuroinvasive property of clusters 2.1 and 2.2 and suggest that enhanced neurovirulence of cluster 2.1 relative to cluster 2.2 is associated with more efficient replication in the central nervous system and in the periphery. Moreover, isolate H induced significantly higher levels of IFN-β, IL-1β, IL-6, TNF-α, Ifit1, and Ifit2 expression relative to isolate Y, indicating a positive correlation between TMUV neurovirulence and magnitude of antiviral innate immune response. The present work demonstrates that the mouse models allow to differentiate between cluster 2.1 and 2.2 isolates and provides mechanistic insights into TMUV-induced disease.
Insights
Tembusu virus (TMUV) cluster 2.1 isolate H is more neurovirulent than cluster 2.2 isolate Y in mice. This difference is linked to higher viral replication and a stronger innate immune response in mice infected with isolate H.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Tembusu virus (TMUV) clusters 2.1 and 2.2 are known to cause lethal neurological disease in mice via intracerebral inoculation.
- Understanding the comparative neurovirulence and replication dynamics of different TMUV strains is crucial for disease mechanism elucidation.
Purpose of the Study:
- To comparatively analyze the clinicopathological outcomes of TMUV cluster 2.1 (isolate H) and cluster 2.2 (isolate Y) infections in mice.
- To investigate the correlation between viral replication, innate immune responses, and neurovirulence of different TMUV isolates.
Main Methods:
- Experimental infection of BALB/c and Kunming mice with TMUV isolates H and Y via subcutaneous (sc) and intracerebral (ic) routes.
- Assessment of clinical signs, mortality, viral replication in brain and spleen, and expression of immune mediators (IFN-β, IL-1β, IL-6, TNF-α, Ifit1, Ifit2).
Main Results:
- Both isolates caused lethal neurological disease upon ic inoculation, with isolate H exhibiting significantly higher neurovirulence than isolate Y.
- Subcutaneous inoculation did not induce disease. Isolate H showed higher replication levels in the brain and spleen compared to isolate Y, particularly after ic inoculation.
- Isolate H induced significantly higher expression of key antiviral innate immune mediators (IFN-β, IL-1β, IL-6, TNF-α, Ifit1, Ifit2) than isolate Y.
Conclusions:
- Mouse models effectively differentiate the neurovirulence of TMUV cluster 2.1 and 2.2 isolates.
- Enhanced neurovirulence of TMUV cluster 2.1 is associated with more efficient viral replication in the central nervous system and periphery, and a heightened innate immune response.
