A recombinant vaccinia virus encoding inducible nitric oxide synthase is attenuated in vivo.
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.
Rolph
M S
MS
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia. michael.rolph@anu.edu.au.
Cowden
W B
WB
Medveczky
C J
CJ
Ramshaw
I A
IA
D000818:Animals; D000998:Antiviral Agents / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007267:Injections; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010053:Ovary / Q000473:pathology / Q000821:virology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester