Inhibition of tumor necrosis factor and interferon triggered responses by DNA viruses

Abstract

DNA viruses use elegant mechanisms to overcome the antiviral responses mediated by tumor necrosis factor (TNF), the TNF receptor family member Fas and the interferons. TNF, which is secreted by activated monocytes and lymphocytes, induces apoptosis as well as expression of genes 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: (1) absorption of extracellular TNF by secreted homologs of the TNF receptor; (2) degradation of Fas; (3) inhibition of the assembly of FADD and Caspase 8 with TNFR1 and Fas; (4) direct inhibition of proapoptotic caspase enzymatic activity; and (5) inhibition of the proapoptotic members of the Bcl-2 family. Interferons induce expression of multiple antiviral genes. DNA viruses encode proteins that function in different ways to block interferon-induced transcription as well as the activity of enzymes that block viral protein synthesis. These antiviral proteins prolong acute and persistent infections.