Replication of respiratory syncytial virus is inhibited in target cells generating nitric oxide in situ.
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.
Ali-Ahmad
Dania
D
Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University, Syracuse, New York 13210, USA.
Bonville
Cynthia A
CA
Rosenberg
Helene F
HF
Domachowske
Joseph B
JB
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects*
D020030:Nitric Oxide Donors; D009573:Nitrites; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010396:Penicillamine