INHIBITORY EFFECT OF NITRIC-OXIDE ON THE REPLICATION OF A MURINE RETROVIRUS IN-VITRO AND IN-VIVO
INHIBITORY EFFECT OF NITRIC-OXIDE ON THE REPLICATION OF A MURINE RETROVIRUS IN-VITRO AND IN-VIVO
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DOI：
10.1128/jvi.69.11.7001-7005.1995
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发表时间：
1995-11-01
影响因子：
5.4
通讯作者：
GOUGEROTPOCIDALO, MA
中科院分区：
文献类型：
--
作者：
AKARID, K;SINET, M;GOUGEROTPOCIDALO, MA
一氧化氮（NO）对包括病毒在内的广谱病原体具有杀微生物作用，但其抗逆转录病毒特性尚未被描述。本研究的目的是确定NO是否在体外抑制小鼠Friend白血病病毒（FV）的复制以及NO在小鼠抵抗FV感染中可能发挥的作用。研究了三种NO产生化合物：3-吗啉代-西多诺亚胺（SIN-1）、硝普钠（SNP）和S-亚硝基-N-乙酰青霉胺（SNAP）。这三种化合物的效果进行了比较，与他们的控制（SIN-1C，铁氰化钾，N-乙酰青霉胺，分别），不产生NO和亚硝酸钠（NaNO 2）。SIN-1、SNP和SNAP以浓度依赖性方式抑制Dunni细胞中FV的复制。相比之下，没有观察到显着的抑制作用与三个控制或NaNO 2。此外，超氧化物歧化酶的加入没有改变SIN-1的抑制作用，SIN-1也已知产生超氧阴离子。在测试的浓度范围内没有观察到Dunni细胞毒性。我们还评估了激活的巨噬细胞产生的NO对FV复制的影响，γ-干扰素和脂多糖激活的巨噬细胞以浓度依赖的方式抑制FV复制。NO合成酶的竞争性抑制剂N-G-硝基-L-精氨酸甲酯（N-G-nitro-L-arginine methyl ester，N-G-nitro-L-arginine methyl ester，N-G-nitro-L-arginine methyl ester）可明显提高FV感染小鼠脾细胞的病毒载量。
Nitric oxide (NO) exerts microbicidal effects on a broad spectrum of pathogens, including viruses, but its antiretrovirus properties have not yet been described. The purpose of this study was to determine whether NO inhibits murine Friend leukemia virus (FV) replication in vitro and to what extent NO may play a role in defenses against FV infection in mice, Three NO-generating compounds were studied: 3-morpholino-sydononimine (SIN-1), sodium nitroprusside (SNP), and S-nitroso-N-acetylpenicillamine (SNAP). The effects of these three compounds were compared with those of their controls (SIN-1C, potassium ferricyanide, and N-acetylpenicillamine, respectively), which do not generate NO and with that of sodium nitrite (NaNO2). SIN-1, SNP, and SNAP inhibited FV replication in dunni cells in a concentration-dependent manner. In contrast, no significant inhibitory effect was observed with the three controls or NaNO2. Furthermore, the addition of superoxide dismutase did not alter the inhibitory effect of SIN-1, which is also known to generate superoxide anions, No dunni cell toxicity was observed in the range of concentrations tested. We also assessed the effect of NO produced by activated macrophages on FV replication, Macrophages activated by gamma interferon and lipopolysaccharide inhibited FV replication in a concentration-dependent manner. This inhibition was due in part to NO production, since it was reversed by N-G-monomethyl L-arginine, a competitive inhibitor of NO synthase, In vivo administration of N-G-nitro-L-arginine methyl ester, a competitive inhibitor of NO synthase, significantly increased the viral load in spleen cells of FV-infected mice, These results suggested that NO may play a role in defenses against the murine Friend leukemia retrovirus.