32 Adenovirus

Abstract

Members of the family Adenoviridae are nonenveloped icosahedral viruses that replicate in the nucleus. Currently, four genera are recognized. The viruses of two genera (i.e., Mastadenovirus and Aviadenovirus) originate from mammals and birds, respectively, whereas the other two genera (Atadenovirus and Siadenovirus) have a broader range of hosts. Members of the Atadenovirus genus infect various ruminant, avian, and reptilian hosts, as well as marsupials. The two known Siadenoviruses were isolated from birds and a frog. An adenovirus (AdV) isolated from sturgeon may be a first member of a distinct fifth genus. Within the genera, the viruses are grouped as “species.” The human adenoviruses (HAdV) are grouped as six species (formerly subgroups), HAdV-A through F, in the Mastadenovirus genus. The evolution and classification of AdV have recently been reviewed (Davison et al. 2003). HAdV contain a linear double-stranded genome of about 36 kb with inverted terminal repetitions of approximately 100 bp. Both 5′ termini are covalently attached to a 55-kD terminal protein (TP). AdV DNA replication is a very efficient process. Infected cells produce approximately one million new copies of viral DNA, equivalent to the cellular DNA content. Because of its efficient replication, AdV has become one of the favorite vectors for mammalian gene transfer and gene therapy.

Details of the replication mechanism have become available thanks to the development of an in vitro system that replicates HAdV-5 and -2 DNA with purified proteins almost as efficiently as in vivo. Two identical origins are located within the inverted terminal repeats, covering...