Herpesviruses have developed strategies to counteract host defenses so as to allow viruses to infect cells and result in a latent or persistent infection. The goal of this project is to identify and determine the function of herpesvirus proteins that interact with host cell proteins to influence the course of infection. These proteins may allow us to identify new molecules that are important in the human immune system. Programmed cell death (apoptosis) is an antiviral defense mechanism used by the host to eliminate virus-infected cells. Some viruses encode proteins that interfere with signalling pathways for apoptosis. We found that two DNA viruses, molluscum contagiosum virus and equine herpesvirus 2, encode proteins with death effector domains (DEDs). Cellular proteins containing DEDs mediate apoptosis signalling pathways. However, unlike the cellular proteins, the viral DED-containing proteins inhibit apoptosis. These viral proteins can bind directly to the cellular proteins and by inhibiting their activity may allow virus-infected cells to escape apoptosis. Epstein-Barr virus (EBV) infects B lymphocytes, causes infectious mononucleosis, and is associated with certain human tumors. EBV encodes a membrane protein termed gp42. We found that gp42 binds to a protein important for recognition by the immune system (the MHC class II HLA-DR beta chain) and inhibits the outgrowth of EBV transformed B cells. A fusion protein containing gp42 also inhibited several immune activities (presentation of antigens and generation of antigen-specific cytotoxic T lymphocytes in mixed lymphocyte cultures). Since gp42 binds to MCH class II HLA-DR, which is present on the surface of B lymphocytes, gp42 may be important for EBV to bind to or penetrate B lymphocytes.
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