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Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication

journal contribution
posted on 2023-05-20, 21:04 authored by Harris, N, Buller, RM, Gunasegaran KarupiahGunasegaran Karupiah
Gamma interferon (IFN-g)-induced nitric oxide synthase (iNOS) and nitric oxide (NO) production in the murine macrophage-like RAW 264.7 cells were previously shown to inhibit the replication of the poxviruses vaccinia virus (VV) and ectromelia virus and herpes simplex virus type 1. In the current study, we performed biochemical analyses to determine the stage in the viral life cycle blocked by IFN-g-induced NO. Antibodies specific for temporally expressed viral proteins, a VV-specific DNA probe, and transmission electron microscopy were used to show that the cytokine-induced NO inhibited late protein synthesis, DNA replication, and virus particle formation but not expression of the early proteins analyzed. Essentially similar results were obtained with hydroxyurea and cytosine arabinoside, inhibitors of DNA replication. Enzymatically active iNOS was detected in the lysates of IFN-g-treated but not in untreated RAW 264.7 cells. The IFN-g-treated RAW 264.7 cells which express iNOS not only were resistant to productive infection but also efficiently blocked the replication of VV in infected bystander cells of epithelial origin. This inhibition was arginine dependent, correlated with nitrite production in cultures, and was reversible by the NOS inhibitor Nv-monomethyl-Larginine.


Publication title

Journal of Virology








Tasmanian School of Medicine


Amer Soc Microbiology

Place of publication

1752 N St Nw, Washington, USA, Dc, 20036-2904

Rights statement

Copyright 1995, American Society for Microbiology

Repository Status

  • Restricted

Socio-economic Objectives

Prevention of human diseases and conditions; Treatment of human diseases and conditions

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