Rolph M S, Cowden W B, Medveczky C J, Ramshaw I A
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
J Virol. 1996 Nov;70(11):7678-85. doi: 10.1128/JVI.70.11.7678-7685.1996.
To investigate the role of nitric oxide during vaccinia virus (VV) infection of mice, a recombinant VV encoding the inducible nitric oxide synthase (iNOS) gene (VV-HA-iNOS) was constructed. Following infection of immunocompromised or immunocompetent mice, the virus was highly attenuated compared with a control recombinant VV. Athymic and sublethally irradiated mice survived infection with 10(7) PFU of VV-HA-iNOS, a dose that resulted in uniform mortality in mice infected with the control recombinant VV. Attenuated virus growth was evident as early as 24 h following infection, suggesting that NO had direct antiviral activity. We have previously shown that treatment of mice with the inhibitor of NO production N(G)-methyl-L-arginine did not influence the course of VV infection in mice. The present study has indicated that NO can potentially exert an antiviral effect during murine VV infection. We propose that during VV infection, nitric oxide production contributes to the control of virus growth, but that in its absence, other antiviral mechanisms are sufficient to mediate fully effective virus clearance.
为了研究一氧化氮在小鼠痘苗病毒（VV）感染过程中的作用，构建了一种编码诱导型一氧化氮合酶（iNOS）基因的重组痘苗病毒（VV-HA-iNOS）。在免疫受损或免疫健全的小鼠感染后，与对照重组痘苗病毒相比，该病毒高度减毒。无胸腺和经亚致死剂量照射的小鼠在感染10(7) PFU的VV-HA-iNOS后存活下来，而该剂量会导致感染对照重组痘苗病毒的小鼠全部死亡。早在感染后24小时就明显出现病毒生长减毒，这表明一氧化氮具有直接的抗病毒活性。我们之前已经表明，用一氧化氮产生抑制剂N(G)-甲基-L-精氨酸处理小鼠并不影响小鼠痘苗病毒感染的进程。本研究表明，在小鼠痘苗病毒感染期间，一氧化氮可能发挥抗病毒作用。我们提出，在痘苗病毒感染期间，一氧化氮的产生有助于控制病毒生长，但在其不存在时，其他抗病毒机制足以介导完全有效的病毒清除。
