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Direct interferon-gamma-mediated protection caused by a recombinant coxsackievirus B3
Andreas Henke1, Roland Zell, Ulrike Martin
1Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Winzerlaer Strasse 10, D-07745 Jena, Germany. i6hean@rz.uni-jena.de
Insights
Recombinant Coxsackievirus B3 expressing interferon-gamma (CVB3(IFN-gamma)) prevents viral myocarditis in mice. This engineered virus reduces viral load, spread, and tissue damage, offering protection against severe CVB3 infection.
Area of Science:
- Virology
- Immunology
- Cardiovascular Research
Background:
- Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis.
- Cytokines play a crucial role in regulating CVB3 replication and disease progression.
- Local cytokine expression via recombinant CVB3 offers a potential strategy for myocarditis prevention.
Purpose of the Study:
- To investigate the protective effects of recombinant CVB3 engineered to express interferon-gamma (IFN-γ) against CVB3-induced viral myocarditis.
- To assess the impact of CVB3(IFN-γ) on viral load, spread, and myocardial tissue damage in a mouse model.
- To evaluate the in vitro efficacy of CVB3(IFN-γ) against homologous and heterologous CVB3 strains.
Main Methods:
- Generation of recombinant CVB3 expressing IFN-γ (CVB3(IFN-γ)).
- Infection of BALB/c and C57BL/6 mice with a highly pathogenic CVB3 variant (CVB3H3) before or after CVB3(IFN-γ) inoculation.
- Assessment of viral load, viral spread, and myocardial tissue destruction.
- In vitro co-cultivation experiments with CVB3(IFN-γ)-infected cells and CVB3H3.
Main Results:
- CVB3(IFN-γ) conferred protection against lethal CVB3H3 infection in mice, significantly decreasing viral load, spread, and tissue destruction.
- The protective effect was observed when CVB3(IFN-γ) was administered shortly before or after the challenge with the pathogenic virus.
- In vitro studies demonstrated that CVB3(IFN-γ)-infected cells reduced CVB3H3 replication and cytopathogenicity, indicating a direct antiviral effect.
- This protective effect was not limited to the homologous virus strain.
Conclusions:
- Local expression of IFN-γ by recombinant CVB3 is a viable strategy for preventing viral myocarditis.
- CVB3(IFN-γ) offers protection through reduced viral burden and tissue damage, with potential applications against various CVB3 strains.
- This approach highlights the therapeutic potential of genetically engineered oncolytic viruses in managing viral heart disease.
Abstract:
Coxsackievirus B3 (CVB3) is one of the most important causes of viral myocarditis. Cytokines are involved in the control of CVB3 replication and pathogenesis. Local expression of specific cytokines by recombinant CVB3 confers prevention of virus-caused myocarditis. Expression of IFN-gamma by CVB3(IFN-gamma) protected BALB/c and C57BL/6 mice when the lethal infection with the highly pathogenic CVB3H3 variant was given directly after or prior to CVB3(IFN-gamma) inoculation by decreasing the viral load and spread as well as tissue destruction. This direct effect was not restricted to the homologous virus. In vitro, cocultivation of CVB3(IFN-gamma)-infected cells induced a reduction of CVB3H3 replication and virus-induced cytopathogenicity.