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The effect of complement depletion on the course of Sindbis virus infection in mice
Insights
Complement component 3 (C3) depletion in mice prolonged Sindbis virus infection, increasing brain viral load and delaying death. Complement plays a dual role in host defense and immunopathology during viral infections.
Area of Science:
- Immunology
- Virology
- Neuroscience
Background:
- Sindbis virus infection is a significant arboviral disease.
- The role of complement system in viral infections is complex and not fully understood.
Purpose of the Study:
- To investigate the role of complement component 3 (C3) in the host response to Sindbis virus infection.
- To determine how C3 depletion affects the course of Sindbis virus infection, including mortality, morbidity, and viral dissemination.
Main Methods:
- BALB/c mice were depleted of C3 using purified cobra venom factor (CoVF).
- Mice were inoculated subcutaneously with Sindbis virus.
- Mortality, morbidity, viral load at the inoculation site, viremia, and brain viral titers were assessed.
Main Results:
- C3 depletion did not alter the mortality rate but delayed the mean day of death.
- Morbidity was prolonged in C3-depleted mice.
- While viral growth at the inoculation site was unchanged, C3-depleted mice exhibited prolonged viremia and a 1000-fold increase in brain viral load at day 6 post-infection.
Conclusions:
- Complement component 3 plays a critical role in controlling Sindbis virus infection.
- Complement contributes to both protective immunity and immunopathology during Sindbis virus infection.
- Targeting the complement system may offer therapeutic strategies for arboviral infections.
Abstract:
The course of Sindbis virus infection in 12-day-old BALB/c mice was altered significantly in animals depleted of the third component of complement (C3) by treatment with purified cobra venom factor (CoVF). Although the same percentage of C3-depleted and normal animals died (30%) after the subcutaneous inoculation of 1000 PFU Sindbis virus, the mean day of death was later in C3-depleted mice (8.4 days) than in controls (6.5 days). In addition, morbidity was prolonged in C3-depleted mice. Growth of virus at the inoculation site in the foot was not different; however, viremia was prolonged and the amount of virus in the brain was 1000-fold greater 6 days after infection in C3-depleted animals. These studies demonstrated that complement plays an important role in the host's response to Sindbis virus infection by participating in both beneficial and immunopathologic responses to the infection.