Antiviral activity of tumor necrosis factor (TNF) is mediated via p55 and p75 TNF receptors.
The antiviral nature of tumor necrosis factor (TNF) is generally well accepted. TNF appears to induce multiple antiviral mechanisms, and to synergize with interferon (IFN)-gamma in promoting antiviral activities. We infected TNF receptor (TNFR)-deficient mice with the virulent murine pathogen, ectromelia virus (EV), and observed that otherwise resistant mice were susceptible to lethal infection. To study the molecular basis of the antiviral action of TNF, mice were infected with a recombinant vaccinia virus encoding murine TNF (VV-HA-TNF). In normal mice, the replication of VV-HA-TNF was highly attenuated. In contrast, mice in which the TNFR type 1 (p55) or the TNFR type 2 (p75) were genetically disrupted showed a moderate defect in their capacity to clear the TNF-encoding virus. The contribution of both TNF receptors to the control of VV-HA-TNF was confirmed by the enhanced replication of VV-HA-TNF in mice deficient for both p55 and p75. These observations were corroborated by infecting TNFR-deficient mice with EV. For both infections, the p55 and p75 TNFRs were necessary to maintain normal levels of resistance. Thus, the antiviral activity of TNF is mediated via both TNFRs in vivo. Furthermore, these studies establish that TNF is an important component of the host response to a natural virus infection.
Ruby
J
J
Viral Engineering and Cytokines Group, Division of Immunology and Cell Biology, John Curtin School of Medical Research, Canberra 2601 Australia. j.ruby@microbiology.unimelb.edu.au
Bluethmann
H
H
Peschon
J J
JJ
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004482:Ectromelia, Infectious / Q000235:genetics / Q000276:immunology / Q000821:virology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D011995:Recombination, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*; D014615:Vaccinia / Q000235:genetics / Q000276:immunology / Q000821:virology; D014616:Vaccinia virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha