9 Oncogenesis by DNA Viruses: Adenovirus

Abstract

I. INTRODUCTION
The adenoviruses are widespread in nature. So far, 31 serotypes have been isolated from humans. They are not important human pathogens. In fact, several adenovirus gene functions suggest they have evolved mechanisms to maintain long-term, inapparent infections of their human hosts.

The adenoviruses contain a 36,000-bp DNA chromosome. Six transcription units are expressed during the early phase of infection, and three late units are activated at the onset of viral DNA replication. Each transcription unit gives rise to a variety of differentially spliced mRNAs. Two of the early units, E1A and E1B, comprise the adenovirus oncogenes (for recent reviews, see Berk 1986; Stillman 1986; Moran and Mathews 1987). All human adenoviruses tested are able to transform cultured rodent fibroblasts, and some serotypes can induce tumors in newborn hamsters and rats.

Like many other DNA tumor virus oncogenes, the adenovirus oncogenes function during normal virus growth. Thus, one of the strengths of the human adenoviruses as an experimental system is that the biochemical functions of their oncogenes can be studied both during viral replication in human cells and within transformed rodent cells.

II. ONCOGENIC POTENTIAL OF ADENOVIRUSES
Human adenoviruses have been divided into five groups, termed A through E, on the basis of DNA homology (Green et al. 1979). These groupings fit well with categorizations based on oncogenicity. Group A adenoviruses (e.g., Ad12, Ad18) are highly oncogenic, inducing tumors in most animals within 4 months; group B members (e.g., Ad3, Ad7) are weakly oncogenic, producing tumors within 4–18...