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Punta Toro virus infection of C57BL/6J mice: a model for phlebovirus-induced disease
1Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21701-5011.
Abstract:
Punta Toro virus infections of inbred strains of mice have been characterized and evaluated as a model in which to study various aspects of the host response to phlebovirus infections and the requirements for protective immunity. The Adames strain of Punta Toro virus was found to be strongly hepatotropic and lymphotropic and the outcome of infection was largely a function of age. C57BL/6J mice of less than 5 weeks of age uniformly developed fulminant hepatocellular necrosis with mean survival times of 4.2 days. Resistance to lethal infection increased with age such that greater than 95% of 8-week-old mice survived challenge. The kinetics of viremia, antibody production, and hematological changes in 4- and 8-week animals indicated that the survival of the older animals is related to their ability to delay virus replication and the development of hepatic lesions during the initial 48 h of infection and their ability to terminate virus replication and clear virus from the circulation 4 to 5 days after infection. The mechanisms responsible for this resistance were studied using anti-interferon serum, immunosuppression, and passive immunization.
Insights
Age significantly impacts Punta Toro virus (PTV) infection outcomes in mice. Older mice develop resistance to PTV by delaying viral replication and clearing the infection, offering insights into phlebovirus immunity.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Punta Toro virus (PTV) is a phlebovirus that causes infections with varying outcomes.
- Inbred mouse strains provide a model to study host responses and protective immunity against phleboviruses.
Purpose of the Study:
- To characterize PTV infections in mice as a model for studying host response and protective immunity.
- To evaluate the role of age in PTV infection severity and survival.
Main Methods:
- Infection of C57BL/6J mice of different ages with the Adames strain of PTV.
- Monitoring of survival, viremia, antibody production, and hematological changes.
- Investigation of resistance mechanisms using anti-interferon serum, immunosuppression, and passive immunization.
Main Results:
- PTV exhibited strong hepatotropism and lymphotropism.
- Younger mice (<5 weeks) experienced fulminant hepatocellular necrosis and rapid mortality (mean survival 4.2 days).
- Older mice (>8 weeks) showed increased resistance, with >95% survival, linked to delayed viral replication and effective viral clearance.
Conclusions:
- Age is a critical determinant of PTV infection outcome in mice.
- Older mice develop resistance through delayed initial viral replication and enhanced viral clearance.
- This model is valuable for understanding phlebovirus pathogenesis and immunity, with potential implications for antiviral strategies.