Nitric oxide and peroxynitrite have different antiviral effects against hantavirus replication and free mature virions
Nitric oxide and peroxynitrite have different antiviral effects against hantavirus replication and free mature virions
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DOI：
10.1002/eji.200535587
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Lundkvist, Ake
中科院分区：
文献类型：
--
作者：
Klingstrom, Jonas;Akerstrom, Sara;Lundkvist, Ake
活性氮中间体（RNI），如一氧化氮（NO）和过氧亚硝酸盐，对某些病毒具有抗病毒作用。汉坦病毒，像布尼亚病毒科的其他成员一样，以前没有显示对RNI敏感。在本研究中，我们比较了一氧化氮和过氧亚硝酸盐对汉坦病毒体外复制、游离成熟病毒粒子和诱导型一氧化氮合酶（iNOS）的影响。生成NO的化合物s -亚硝基-n -乙酰青霉胺（SNAP）以及细胞因子诱导的NO均能强烈抑制汉坦病毒在Vero E6细胞中的复制，而用SNAP预处理游离病毒粒子对其活性的影响有限。相比之下，作为过氧亚硝酸盐供体的3- morpholinosydnon亚胺盐酸盐（SIN-1）在体外仅能很低程度地抑制病毒复制，但用SIN-1预处理病毒会导致病毒粒子的活力大大降低。感染各种人类细胞类型本身不诱导NO的产生。iNOS（-/-）小鼠体内的病毒滴度高于对照组，表明No抑制汉坦病毒在体内的复制。综上所述，我们发现NO对汉坦病毒复制具有较强的抗病毒作用，而过氧亚硝酸盐对成熟的游离病毒粒子具有较强的抗病毒作用，这表明不同的RNI对同一病毒复制周期的不同部分具有不同的作用。
Reactive nitrogen intermediates (RNI), like nitric oxide (NO) and peroxynitrite, have antiviral effects against certain viruses. Hantaviruses, like other members of the Bunyaviridae family, have previously not been shown to be sensitive to RNI. In this study, we compared the effects of NO and peroxynitrite on hantavirus replication and free mature virions in vitro, and of inducible nitric oxide synthase (iNOS) in hantavirus-infected suckling mice. The NO-generating compound S-nitroso-N-acetylpenicillamine (SNAP), as well as cytokine-induced NO, strongly inhibited hantavirus replication in Vero E6 cells, while pretreatment of free virions with SNAP only had a limited effect on their viability. In contrast, 3-morpholinosydnonimine hydrochloride (SIN-1), a peroxynitrite donor, inhibited virus replication only to a very low extent in vitro, but pretreatment of virus with SIN-1 led to a considerably lowered viability of the virions. Infections of various human cell types per se did not induce NO production. The viral titers in iNOS(-/-) mice were higher compared to the controls, suggesting that No inhibits hantavirus replication in vivo. In conclusion, we show that NO has strong antiviral effects on hantavirus replication, and peryoxynitrite on mature free virions, suggesting that different RNI can have different effects on various parts of the replication cycle for the same virus.