Antiviral activity of tumor necrosis factor is signaled through the 55-kDa type I TNF receptor [corrected].
Agonist antibodies (Ab) to the two TNF receptors, TNF-R1 (55 kDa) and TNF-R2 (75 kDa), have been shown to signal many of the distinct functions induced by TNF-alpha. We have found that anti-TNF-R1, but not anti-TNF-R2, Ab trigger antiviral activity in human hepatoma Hep-G2 cells and enhance the antiviral activity of IFN-gamma in human lung fibroblast A549 cells. Likewise, anti-human-TNF-R1 Ab had antiviral enhancing activity on murine L929 cells engineered to express human TNF-R1. However, L929 cells that express human TNF-R1 lacking most of the intracellular domain fail to respond to anti-human-TNF-R1 Ab. This demonstrates that the intracellular domain of TNF-R1 is necessary to generate antiviral activity. TNF-R1 but not TNF-R2 also signals killing of virus-infected cells by TNF-alpha. Thus, all the known antiviral activities of TNF-alpha are mediated through TNF-R1.
Wong
G H
GH
Department of Immunology, Genentech, Inc., South San Francisco, CA 94080.
Tartaglia
L A
LA
Lee
M S
MS
Goeddel
D V
DV
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma