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Lethal role of interferon in lymphocytic choriomeningitis virus-induced encephalitis
Abstract:
After intracerebral inoculation of adult C3H mice, the 'docile' strain of lymphocytic choriomeningitis (LCM) virus multiplied to high titre in several visceral organs. Although the virus content of lung, liver, spleen and brain was high, these mice did not die but became long-term carriers of the virus. Injection of mice with the same dose of the 'aggressive' strain of LCM virus resulted in much lower virus titres in these organs; nevertheless, 100% of the mice died within 7 to 9 days. The results presented here show that mice infected with the 'aggressive' virus do not die if treated with anti-interferon globulin. Under these conditions the titres of 'aggressive' virus were as high in the different organs as in mice injected with the 'docile' virus. These results are consistent with the hypothesis that inhibition of LCM virus multiplication in various organs by interferon results in a lethal disease. The possible mechanisms underlying this seemingly paradoxical phenomenon are discussed.
Insights
The aggressive strain of lymphocytic choriomeningitis (LCM) virus caused rapid death in mice, while a docile strain led to long-term carriers. Interferon inhibition of the aggressive strain paradoxically prevented death, increasing viral load.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Lymphocytic choriomeningitis (LCM) virus exhibits varying pathogenicity.
- Interferon plays a crucial role in antiviral defense.
Purpose of the Study:
- To investigate the role of interferon in LCM virus pathogenesis.
- To understand the paradoxical lethality associated with the 'aggressive' LCM virus strain.
Main Methods:
- Intracerebral inoculation of C3H mice with 'docile' and 'aggressive' LCM virus strains.
- Treatment of mice with anti-interferon globulin.
- Quantification of viral titres in various organs (lung, liver, spleen, brain).
Main Results:
- 'Docile' LCM virus strain caused high viral titres and long-term carrier state without mortality.
- 'Aggressive' LCM virus strain resulted in rapid death despite lower initial viral titres.
- Anti-interferon globulin treatment prevented death from the 'aggressive' strain, leading to high viral titres similar to the 'docile' strain.
Conclusions:
- Interferon-mediated inhibition of LCM virus replication may paradoxically contribute to disease lethality.
- Interferon's role in LCM virus infection is complex, influencing both viral control and host survival.
- Further research is needed to elucidate the mechanisms behind interferon's paradoxical effect in this model.