Antiviral action of tumor necrosis factor in human fibroblasts is not mediated by B cell stimulatory factor 2/IFN-beta 2, and is inhibited by specific antibodies to IFN-beta.
A protein termed IFN-beta 2, originally described on the basis of antiviral activity and antigenic cross-reactivity with the classical IFN-beta, is now known to be identical with the independently isolated B cell stimulatory factor (BSF-2). Earlier it was suggested that IFN-beta 2 (i.e., BSF-2) mediates the antiviral action of TNF in human fibroblasts. We examined Escherichia coli-derived recombinant preparations of human IFN-beta and BSF-2 for antiviral activity and plasmacytoma growth factor (PCT-GF) activity. IFN-beta had antiviral activity but showed no PCT-GF activity. BSF-2 showed potent PCT-GF activity but lacked antiviral activity. Antiviral activity of IFN-beta was neutralized by polyclonal antibodies and mAb to IFN-beta, but not by antibody to rBSF-2. PCT-GF activity of BSF-2 was neutralized by antibody to rBSF-2, but not by antibodies neutralizing the antiviral action of IFN-beta. Five mAb and a polyclonal antibody to human IFN-beta failed to react with BSF-2 in a solid phase RIA and antibody to BSF-2 did not react with IFN-beta. PCT-GF activity in supernatants of human FS-4 fibroblasts stimulated with TNF, IL-1 or poly(I).poly(C) was neutralized by antibody to rBSF-2, but not by antibodies neutralizing the antiviral activity of IFN-beta. Finally, the antiviral activity of TNF in FS-4 cultures was neutralized by antibodies to IFN-beta but not by antibodies to BSF-2. Taken together, these results support the view that the antiviral action of TNF in human fibroblasts is mediated by IFN-beta, and not by BSF-2/IFN-beta 2 that apparently lacks significant antiviral activity.
Reis
L F
LF
Department of Microbiology, New York University Medical Center 10016.
Le
J M
JM
Hirano
T
T
Kishimoto
T
T
Vilcek
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002460:Cell Line; D002474:Cell-Free System; D004926:Escherichia coli; D005347:Fibroblasts / Q000502:physiology*; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000494:pharmacology*; D008222:Lymphokines / Q000502:physiology; D051379:Mice; D011994:Recombinant Proteins / Q000502:physiology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D006133:Growth Substances; D007370:Interferon Type I; D015850:Interleukin-6; D007378:Interleukins; D008222:Lymphokines; D011994:Recombinant Proteins