Mechanisms of cytokine-mediated inhibition of viral replication.
In this report, the role of nitric oxide synthase (NOS) and IL-12 administration in inhibition of vesicular stomatitis virus (VSV) from infected neuroblastoma cells was examined. We previously have shown that cytokine treatment of cells results in the induction of NOS-1, and this is associated with a 2 log inhibition of VSV production. We performed these studies to examine the mechanism by which viral replication is suppressed. Neuroblastoma cells (NB41A3) were treated with either IL-12 or medium and subsequently infected with VSV. Viral protein and mRNA were isolated from these cells, and their levels were measured by Western or Northern blots, respectively. mRNA levels were decreased modestly, but viral proteins were decreased substantially in cells pretreated with IL-12, suggesting that the inhibitory effect of NO is working at the translational level. Cytokine treatment of cells was not associated with oxidative stress. The viral proteins also were nitrosylated. These data suggest that the mechanism of NO inhibition of viral replication occurs through translational interference and posttranslational modifications of viral components.
Komatsu
T
T
Department of Biology, Center for Neural Science, Kaplan Comprehensive Cancer Center, New York University, 100 Washington Square East, New York City, New York, 10003-6688, USA.
Srivastava
N
N
Revzin
M
M
Ireland
D D
DD
Chesler
D
D
Reiss
C S
CS
D015152:Blotting, Northern; D015153:Blotting, Western; D016207:Cytokines / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D009447:Neuroblastoma; D009474:Neurons / Q000821:virology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects
D016207:Cytokines; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; D018664:Interleukin-12; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase