Interferon-gamma-induced activation of nitric oxide-mediated antiviral activity of macrophages caused by a recombinant coxsackievirus B3.
Cardiovascular disease is one of the major causes of human death and has been linked to many different risks including viral infections. Coxsackievirus B3 (CVB3) is one of the most important pathogens responsible for virus-induced myocarditis. Cytokines are normally involved in the control of CVB3 replication and pathogenesis. Among them, interferon-gamma (IFN-gamma) in particular is highly protective against CVB3. A novel strategy to circumvent virus-caused heart disease is based on the development of cytokine-expressing recombinant virus vectors. Using in vitro co-culture experiments, the release of IFN-gamma by the recombinant virus variant CVB3/IFN-gamma activates the expression of the inducible nitric oxide synthase (iNOS) in CVB3 non-susceptible murine macrophages and the release of nitric oxide (NO), which reduce coxsackieviral replication directly. In addition, the expression of IFN-gamma by CVB3/IFN-gamma contributes to protect mice from lethal infections by iNOS induction in murine peritoneal macrophages, viral load reduction, and pancreatic tissue protection.
Jarasch
Nadine
N
Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Hans-Knöll-Str. 2, D-07745 Jena, Germany.
Martin
Ulrike
U
Kamphausen
Esther
E
Zell
Roland
R
Wutzler
Peter
P
Henke
Andreas
A
D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004769:Enterovirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011995:Recombination, Genetic
D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse