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Postinfection therapy of arbovirus infections in mice
I P Singh1, D H Coppenhaver, M Sarzotti
1Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
Abstract:
Most antiviral agents are efficacious prophylactically in vivo, and a few are efficacious for postinfection (p.i.) therapy. To explore possibilities for p.i. therapy of encephalogenic Banzi virus (BZV) and Semliki Forest virus infections in mice, we evaluated candidate antiviral therapies after development of the first clinical signs of infection. The earliest clinical indication of BZV viremia in mice is a rise in core body temperature beginning on day 3 p.i. BZV-infected mice showing elevated core body temperatures (greater than or equal to 37.3 degrees C) on days 3 and 4 p.i. were treated intraperitoneally with the interferon inducer poly(ICLC) (80 micrograms per mouse) and/or specific antiserum. Combined therapy on day 3 of a BZV infection protected over 75% of mice showing clinical evidence of viral disease before treatment. Protection against early brain infection must occur on day 4 p.i., since by that day BZV has started multiplying in the brains of the mice. Significant protection occurred with antiserum alone and increased with poly(ICLC). Similar protection was obtained during Semliki Forest virus viremia, but this infection is so rapid that the first clinical signs are reliably detectable only after viremia.
Insights
Post-infection therapy with poly(ICLC) and antiserum protected mice against Banzi virus (BZV) and Semliki Forest virus infections. Combined treatment was most effective when initiated early after symptom onset.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Most antiviral drugs are effective preventatively, with fewer options for post-infection treatment.
- Encephalogenic viruses like Banzi virus (BZV) and Semliki Forest virus pose significant therapeutic challenges.
- Early intervention is critical for managing viral infections, especially those affecting the central nervous system.
Purpose of the Study:
- To investigate the efficacy of post-infection antiviral therapies for BZV and Semliki Forest virus in mouse models.
- To evaluate the potential of poly(ICLC) and specific antiserum as therapeutic agents after the onset of clinical signs.
- To determine the optimal timing for initiating antiviral treatment to maximize protection.
Main Methods:
- Mice infected with BZV or Semliki Forest virus were treated after the appearance of clinical symptoms.
- Therapies included the interferon inducer poly(ICLC) and specific antiviral antiserum, administered intraperitoneally.
- Treatment efficacy was assessed based on survival rates and protection against viral disease progression.
Main Results:
- Combined therapy with poly(ICLC) and antiserum protected over 75% of BZV-infected mice exhibiting clinical signs.
- Antiserum alone provided significant protection, which was enhanced by the addition of poly(ICLC).
- Similar protective effects were observed in Semliki Forest virus infections, although rapid disease progression complicated early treatment.
Conclusions:
- Post-infection therapy, particularly combination treatment, can be effective against BZV and Semliki Forest virus infections.
- Early administration of antiviral agents, guided by clinical indicators like fever, is crucial for successful treatment outcomes.
- Poly(ICLC) in conjunction with specific antiserum shows promise for managing viral encephalitis when initiated promptly after symptom detection.
