Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente

C A Benedict, T A Banks, L Senderowicz, M Ko, W J Britt, A Angulo, P Ghazal, C F Ware

Research output: Contribution to journalArticlepeer-review


Tumor necrosis factor (TNF)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (CMV), to evolve counterstrategies in order to persist in immune-competent hosts. Signaling by the lymphotoxin (LT)-beta receptor or TNF receptor-1, but not Fas or TRAIL receptors, inhibits the cytopathicity and replication of human CMV by a nonapoptotic, reversible process that requires nuclear factor kappa B (NF-kappa B)-dependent induction of interferon-beta (IFN-beta). Efficient induction of IFN-beta requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LT alpha-deficient mice and LT beta R-Fc transgenic mice were profoundly susceptible to murine CMV infection. Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV.
Original languageEnglish
Pages (from-to)617-26
Number of pages10
JournalInfection and Immunity
Issue number4
Publication statusPublished - 2001


  • Adaptor Proteins, Signal Transducing
  • Animals
  • Carrier Proteins
  • Cells, Cultured
  • Cytomegalovirus
  • Fas-Associated Death Domain Protein
  • Herpesviridae Infections
  • Host-Parasite Interactions
  • Humans
  • Interferon-beta
  • Lymphotoxin beta Receptor
  • Lymphotoxin-alpha
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Muromegalovirus
  • NF-kappa B
  • Proteins
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Survival Rate
  • TNF Receptor-Associated Factor 3
  • Transcriptional Activation
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha
  • Virus Replication


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