Ali-Ahmad Dania, Bonville Cynthia A, Rosenberg Helene F, Domachowske Joseph B
Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
Front Biosci. 2003 Jan 1;8:a48-53. doi: 10.2741/986.
Nitric oxide (NO) is generated by recruited inflammatory cells and by pulmonary epithelial cells in response to respiratory virus infection, although the relative antiviral efficacy of NO from each of these sources had not been clarified. To compare the direct, antiviral potency of NO from an exogenous source with that generated by target epithelial cells in situ, we transduced HEp-2 epithelial cells with the retroviral construct, pMFGS-NOS and cloned transductant lines that generated NO constitutively. We found that NO-producing HEp-2 cells could be infected with RSV, but the titer correlated inversely with NO production, an effect that was reversed by the NOS inhibitor, NG-methyl-L-arginine (NGMMA). Our results demonstrate that NO has significant direct antiviral activity against RSV, and interestingly, that the inhibitory effect is more potent in the presence of continuous, endogenous NO production than in response to NO from an exogenous source.
一氧化氮（NO）由募集的炎症细胞和肺上皮细胞在呼吸道病毒感染时产生，尽管来自这些来源的NO的相对抗病毒功效尚未明确。为了比较外源性NO与原位靶上皮细胞产生的NO的直接抗病毒效力，我们用逆转录病毒构建体pMFGS-NOS转导HEp-2上皮细胞，并克隆了组成性产生NO的转导细胞系。我们发现产生NO的HEp-2细胞可以被呼吸道合胞病毒（RSV）感染，但病毒滴度与NO产生呈负相关，一氧化氮合酶（NOS）抑制剂NG-甲基-L-精氨酸（NGMMA）可逆转这种效应。我们的结果表明，NO对RSV具有显著的直接抗病毒活性，有趣的是，与外源性NO相比，持续内源性NO产生时的抑制作用更强。
