Nitric oxide inhibits Marek's disease virus replication but is not the single decisive factor in interferon-gamma-mediated viral inhibition.
The purpose of this study was to determine to what extent nitric oxide (NO) may play a role in the antiviral-mediated effect of chicken IFN-gamma against the Marek's disease virus (MDV) RB-1B. NO-generating compounds S-nitroso-N-acetylpenicillamine (SNAP) and 3-morpholino-sydononimine (SIN-1) strongly inhibited RB-1B replication in chicken embryo fibroblasts (85%) in a dose-dependent manner. The addition of superoxide dismutase (SOD) did not alter the inhibitory effect of SIN-1, which is also known to generate superoxide anions. IFN-gamma-stimulated embryo fibroblasts almost totally suppressed viral replication and were high NO producers. Nevertheless, addition of N(G)-monomethyl-l-arginine (l-NMMA), a competitive inhibitor of NO synthase, inhibited NO production without preventing the dramatic viral suppression. IFN-gamma-stimulated chicken bone-marrow macrophages were good NO producers and demonstrated a specific cell dose-related inhibiting effect on RB-1B replication in bystander fibroblasts (around 60% at 10(6) macrophages). Adding l-NMMA together with oxygen scavengers such as SOD or d-mannitol restored viral replication almost completely. In conclusion, NO alone is a powerful inhibitor of MDV replication in chicken fibroblasts. Nevertheless, NO is not responsible for the direct inhibitory effect of the IFN-gamma treatment of fibroblasts and is only partially involved in the inhibitory effect of IFN-gamma-stimulated macrophages, which is also mediated by reactive oxygen intermediates.
Djeraba
A
A
Laboratoire de Virologie et Oncologie Aviaire, INRA, Nouzilly, 37380, France.
Bernardet
N
N
Dambrine
G
G
Quéré
P
P
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D019556:COS Cells; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D005347:Fibroblasts; D008381:Herpesvirus 2, Gallid / Q000187:drug effects / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008264:Macrophages / Q000502:physiology / Q000821:virology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D020030:Nitric Oxide Donors; D013481:Superoxides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D007371:Interferon-gamma; D008981:Molsidomine; D013482:Superoxide Dismutase; D010396:Penicillamine