Adenovirus–Host Interactions to Subvert the Host Immune System
William S. M. Wold and Ann E. Tollefson
Viruses have evolved ingenious mechanisms to evade the host antiviral response. The first to be recognized is antigenic variation, which allows viruses to escape preexisting antibodies, and is exemplified by influenza virus epidemics that occasionally sweep across the world. Essentially every antiviral response that we can imagine is targeted by different viruses, including inhibition of cytokine and chemokine responses, killer immune cell activity, apoptosis (programmed cell death), shut-off of cellular protein synthesis, and regulation of cellular gene expression. These viral anti-host proteins are fascinating because they teach us about the immune system, cell and molecular biology, and viral pathogenesis. They also teach how to design gene therapy vectors which, of course, face many of the same obstacles as wild type viruses. Further, it may be possible to use viral proteins in vectors to blunt the host response to the vector. In this article we will discuss adenovirus (Ad) proteins that counteract host responses. Most of these proteins are coded by the E3 transcription unit (Fig. 26.1), a cassette of genes expressed throughout Ad infection. These proteins are presumed to prolong acute Ad infections, thereby providing more opportunity for the virus to replicate, and to permit long term persistent Ad infection.