Djeraba A, Bernardet N, Dambrine G, Quéré P
Laboratoire de Virologie et Oncologie Aviaire, INRA, Nouzilly, 37380, France.
Virology. 2000 Nov 10;277(1):58-65. doi: 10.1006/viro.2000.0576.
The purpose of this study was to determine to what extent nitric oxide (NO) may play a role in the antiviral-mediated effect of chicken IFN-gamma against the Marek's disease virus (MDV) RB-1B. NO-generating compounds S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholino-sydononimine (SIN-1) strongly inhibited RB-1B replication in chicken embryo fibroblasts (85%) in a dose-dependent manner. The addition of superoxide dismutase (SOD) did not alter the inhibitory effect of SIN-1, which is also known to generate superoxide anions. IFN-gamma-stimulated embryo fibroblasts almost totally suppressed viral replication and were high NO producers. Nevertheless, addition of N(G)-monomethyl-l-arginine (l-NMMA), a competitive inhibitor of NO synthase, inhibited NO production without preventing the dramatic viral suppression. IFN-gamma-stimulated chicken bone-marrow macrophages were good NO producers and demonstrated a specific cell dose-related inhibiting effect on RB-1B replication in bystander fibroblasts (around 60% at 10(6) macrophages). Adding l-NMMA together with oxygen scavengers such as SOD or d-mannitol restored viral replication almost completely. In conclusion, NO alone is a powerful inhibitor of MDV replication in chicken fibroblasts. Nevertheless, NO is not responsible for the direct inhibitory effect of the IFN-gamma treatment of fibroblasts and is only partially involved in the inhibitory effect of IFN-gamma-stimulated macrophages, which is also mediated by reactive oxygen intermediates.
本研究的目的是确定一氧化氮（NO）在鸡γ干扰素抗马立克氏病病毒（MDV）RB - 1B的抗病毒介导效应中可能发挥的作用程度。产生NO的化合物S - 亚硝基 - N - 乙酰青霉胺（SNAP）和3 - 吗啉代 - 西多诺明（SIN - 1）以剂量依赖的方式强烈抑制鸡胚成纤维细胞中RB - 1B的复制（85%）。添加超氧化物歧化酶（SOD）并未改变SIN - 1的抑制作用，已知SIN - 1也会产生超氧阴离子。γ干扰素刺激的胚成纤维细胞几乎完全抑制病毒复制，并且是NO的高产者。然而，添加NO合酶的竞争性抑制剂N（G）- 单甲基 - L - 精氨酸（L - NMMA）可抑制NO产生，但并未阻止显著的病毒抑制作用。γ干扰素刺激的鸡骨髓巨噬细胞是良好的NO生产者，并对旁观者成纤维细胞中RB - 1B的复制表现出特定的细胞剂量相关抑制作用（在10^6个巨噬细胞时约为60%）。将L - NMMA与诸如SOD或D - 甘露醇等氧清除剂一起添加几乎完全恢复了病毒复制。总之，单独的NO是鸡成纤维细胞中MDV复制的强大抑制剂。然而，NO并不负责γ干扰素对成纤维细胞的直接抑制作用，并且仅部分参与γ干扰素刺激的巨噬细胞的抑制作用，该抑制作用也由活性氧中间体介导。
