16 Viral DNA Polymerases

Abstract

Because many viruses are readily amenable to molecular, genetic, and biochemical analyses, and because the replication of certain viruses has been the target of antiviral drug development, a wealth of information has accumulated regarding the structure, functions, properties, and regulation of eukaryotic viral DNA polymerases. Viral DNA polymerases have interesting similarities with eukaryotic cellular DNA polymerases (Wang, this volume) and fascinating differences, both of which shed light on mechanisms of polymerase function.

With the exception of the papovaviruses and parvoviruses, which utilize cellular DNA polymerases for their replication, all known DNA viruses that infect animal cells encode their own DNA polymerases. In each case, the DNA polymerase is essential for the replication of the virus. Why have these viruses evolved to encode and require their own DNA polymerases? (In this chapter, only DNA polymerases that strictly utilize DNA templates are considered. Information about the reverse transcriptases encoded by retroviruses or the polymerases encoded by hepadnaviruses can be found in Skalka and Goff [1993] and in Seeger and Mason [this volume].) For poxviruses, which replicate in the cytoplasm (Traktman, this volume), the answer may be that the viral genome does not gain access to the cellular polymerases. For other viruses, the answer may be that their normal life cycles entail the productive infection of nondividing cells that do not express sufficient cellular polymerase.

Despite the fact that these viruses have each evolved a unique DNA polymerase that cannot be replaced by cellular polymerases, the viral enzymes share considerable sequence homology with...