Early Gene Expression
Philip E. Branton
The major targets of human adenoviruses are terminally differentiated epithelial cells of the upper respiratory tract, gut and eye. Once the virus has entered the cell and its DNA uncoated appropriately, progression of the infectious cycle depends on the ability of the virus to solve several problems. One is the need to express early viral genes, and this function relies largely on a powerful transcriptional activator, the early region 1A (E1A) protein that amplifies expression of the E1A gene and that of all other early transcription units encoding functions necessary to drive viral replication. A second is the need to stimulate the infected cell to enter S-phase. Adenoviruses encode only a limited number of functions and must rely on host cell machinery to replicate viral DNA. E1A products serve this function as well, and are able to coax resting or differentiated cells to re-enter the cell cycle. As will be discussed, an unavoidable consequence of E1A expression is the activation of programmed cell death, and thus adenoviruses have evolved a number of strategies to avoid early apoptosis that would severely limit production of progeny virions. Nevertheless, adenoviruses use apoptosis later in infection to facilitate release of progeny, and thus must play a complex balancing act between induction and suppression of apoptosis to optimize infection. Other challenges include the need to convert infected cells into factories that mass produce viral products, and the necessity to counter attempts by the cell to block replication, including production of antiviral molecules like interferon and induction of immune and inflammatory responses. As we will see, adenoviruses encode a number of products that lessen or eliminate these effects. In this chapter we will review details of early adenovirus products and their role in viral replication.