Lymphotoxins and cytomegalovirus cooperatively induce interferon-β, establishing host-virus Détente

Academic Article


  • 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)-β 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 κB (NF-κB)-dependent induction of interferon-β (IFN-β). Efficient induction of IFN-β requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LTα-deficient mice and LTβR-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.
  • Published In

  • Immunity  Journal
  • Digital Object Identifier (doi)

    Author List

  • Benedict CA; Banks TA; Senderowicz L; Ko M; Britt WJ; Angulo A; Ghazal P; Ware CF
  • Start Page

  • 617
  • End Page

  • 626
  • Volume

  • 15
  • Issue

  • 4