The antiviral activity of tumour necrosis factor on herpes simplex virus type 1: role for a butylated hydroxyanisole sensitive factor.
We have previously shown that specific antibodies (Mab 32/Ab 301) against tumour necrosis factor (TNF) enhance its antiviral activity in vaccinia virus-infected mice. In the present study, TNF alone was found to have antiviral activity against herpes simplex virus-1 (HSV-1). Antibody enhancement was found, both in vivo and in vitro, at lower TNF doses. The magnitude of the TNF-induced antiviral response was dependent upon the genetic background of the mouse. C57BL/6 mice were very sensitive to the antiviral activity of TNF, which was inhibited by the free radical scavenger butylated hydroxyanisole (BHA). TNF plus Mab 32 induced a significant antiviral effect in L929 cells which was associated with pronounced CPE. The CPE was largely reversed in the presence of BHA, and furthermore, TNF antiviral activity was significantly reversed in the presence of BHA. Specific inhibitors of nitric oxide synthetase, lipoxygenase or cyclo-oxygenase did not influence either the CPE or growth kinetics of HSV-1, suggesting that neither reactive nitrogen intermediates nor arachidonic acid metabolites were involved in the antiviral mechanism of TNF. This, together with observed increases in Cu/Zn SOD levels in virus infected cells, suggests that reactive oxygen intermediates may have a role in the direct control of HSV-1 growth and that free radicals may play a part in the antiviral activity induced by TNF.
Lidbury
B A
BA
Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Ramshaw
I A
IA
Rolph
M S
MS
Cowden
W B
WB
D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral; D005260:Female; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D014409:Tumor Necrosis Factor-alpha; D002083:Butylated Hydroxyanisole; D013482:Superoxide Dismutase