Jarasch Nadine, Martin Ulrike, Kamphausen Esther, Zell Roland, Wutzler Peter, Henke Andreas
Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Hans-Knöll-Str. 2, D-07745 Jena, Germany.
Viral Immunol. 2005;18(2):355-64. doi: 10.1089/vim.2005.18.355.
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.
心血管疾病是人类死亡的主要原因之一，并且与包括病毒感染在内的许多不同风险相关联。柯萨奇病毒B3（CVB3）是导致病毒诱导性心肌炎的最重要病原体之一。细胞因子通常参与CVB3复制和发病机制的控制。其中，γ干扰素（IFN-γ）对CVB3具有高度保护作用。一种规避病毒引起的心脏病的新策略基于表达细胞因子的重组病毒载体的开发。通过体外共培养实验，重组病毒变体CVB3/IFN-γ释放的IFN-γ激活了CVB3不敏感的小鼠巨噬细胞中诱导型一氧化氮合酶（iNOS）的表达以及一氧化氮（NO）的释放，这直接减少了柯萨奇病毒的复制。此外，CVB3/IFN-γ表达的IFN-γ通过在小鼠腹膜巨噬细胞中诱导iNOS、降低病毒载量和保护胰腺组织，有助于保护小鼠免受致命感染。
