Interferon-beta suppresses herpes simplex virus type 1 replication in trigeminal ganglion cells through an RNase L-dependent pathway.
The induction of an antiviral state by type I interferons (IFN) was evaluated in primary trigeminal ganglion cell cultures using herpes simplex virus type 1 (HSV-1). Cells treated with mouse IFN-beta consistently showed the greatest resistance to HSV-1 infection in comparison to cells treated with IFN-alpha1, IFN-alpha4, IFN-alpha5, IFN-alpha6, or IFN-alpha9. The antiviral efficacy was dose-dependent and correlated with the induction of the IFN-inducible, antiviral genes, 2'-5' oligoadenylate synthetase (OAS) and double-stranded RNA-dependent protein kinase. In trigeminal ganglion cells deficient in the downstream effector molecule of the OAS pathway, RNase L, the antiviral state induced by IFN-beta was lost.
Carr
Daniel J J
DJ
Department of Ophthalmology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dan-carr@ouhsc.edu
Al-khatib
Khaldun
K
James
Cassandra M
CM
Silverman
Robert
R
D000818:Animals; D000998:Antiviral Agents / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D016130:Immunophenotyping; D016899:Interferon-beta / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D012668:Trigeminal Ganglion / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000821:virology*; D014709:Vero Cells; D014779:Virus Replication / Q000235:genetics / Q000276:immunology*
D000998:Antiviral Agents; D016899:Interferon-beta; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease