Human adenoviruses: Evading detection by cytotoxic T lymphocytes

Human adenoviruses cause lytic and persistent respiratory, enteric, and oth er infections. Adenoviruses can transform primary rodent cells and certain serotypes of human adenoviruses (such as adenovirus type 12 from subgenus A ) induce tumors in newborn rodents. In both cases, adenovirus gene products mediate evasion of the cellular immune system by infected and tumor cells. In viral infection, a product of the early region E3 gene, a glycoprotein termed E3-19K, binds to and retains newly synthesised major histocompatibil ity complex (MHC) class I molecules in the endoplasmic reticulum thus rende ring infected cells resistant to lysis by cytotoxic T lymphocytes. In addit ion, other products of the E3 region confer on infected cells resistance to tumor necrosis factor-alpha-mediated lysis. Not all human adenovirus serot ypes encode an E3-19K protein: viruses from subgenus A (such as adenovirus 12) and F (the enteric adenoviruses 40 and 41) do not encode an E3-19K mole cule. In the case of Ad12, products of the viral EIA gene repress MHC class I heavy chain gene transcription. This leads to loss of MHC class I molecu les from the surface of adenovirus 12-transformed cells and contributes to their evasion from cytotoxic T lymphocytes. Considerable progress has been made toward identifying the targets for E1A-mediated repression of the clas s I heavy chain promoter In addition, adenovirus 12 mediates transcriptiona l repression of other genes in the MHC complex involved in antigen presenta tion, namely the transporter associated with antigen presentation (TAP) gen es and MHC-encoded proteasome components, the low molecular weight proteins termed LMPs. Overall, adenoviruses display a variety of differing mechanis ms for posttranslational (E3-19K) and transcriptional (E1A) repression of M HC class I expression that operate in all human viral serotypes studied, su ggesting that evasion of cytotoxic T cell lysis forms an important part of the infection and oncogenic transformation strategies adopted by human aden oviruses. (C) 1998 Academic Press.