INHIBITION OF TUMOR-NECROSIS-FACTOR AND INTERFERON TRIGGERED RESPONSES BY DNA VIRUSES

DNA vi viruses use elegant mechanisms to overcome the antiviral respon ses mediated by tumor necrosis factor (TNF), the TNF receptor family m ember Fas and the interferons. TNF, which is secreted by activated mon ocytes and lymphocytes, induces apoptosis as well as expression of gen es involved in the inflammatory and immune responses. Depending on the DNA virus and the viral proteins, the following mechanisms to prevent TNF receptor- and Fas-induced apoptosis are used: (I) absorption of e xtracellular TNF by secreted homologs of the TNF receptor; (2) degrada tion of Fas; (3) inhibition of the assembly of FADD and Caspase 8 with TNFR1 and Fas; (4) direct inhibition of proapoptotic caspase enzymati c activity; and (5) inhibition of the proapoptotic members of the Bcl- 2 family. Interferons induce expression of multiple antiviral genes. D NA viruses encode proteins that function in different ways to block in teferon-induced transcription as well as the activity of enzymes that block viral protein synthesis. These antiviral proteins prolong acute and persistent infections.