THE EVOLUTION OF SMALL DNA VIRUSES OF EUKARYOTES - PAST AND PRESENT CONSIDERATIONS

Historically, viral evolution has often been considered from the persp ective of the ability of the virus to maintain viral pathogenic fitnes s by causing disease. A predator-prey model has been successfully appl ied to explain genetically variable quasi-species of viruses, such as influenza virus and human immunodeficiency virus (HIV), which evolve m uch faster rates than the host. In contrast, small DNA viruses (polyom aviruses, papillomaviruses, and parvoviruses) are species specific but are stable genetically, and appear to have co-evolved with their host species. Genetic stability is attributable primarily to the ability t o establish and maintain a benign persistent state in vivo and not to the host DNA proofreading mechanisms. The persistent state often invol ves a cell cycle-regulated episomal state and a tight linkage of DNA a mplification mechanisms to cellular differentiation. This linkage requ ires conserved features among viral regulatory proteins, with characte ristic host-interactive domains needed to recruit and utilize host mac hinery, thus imposing mechanistic constrains on possible evolutionary options. Sequence similarities within these domains are seen amongst a ll small mammalian DNA viruses and most of the parvo-like viruses, inc luding those that span the entire spectrum of evolution of organisms f rom E. coli to humans that replicate via a rolling circle-like mechani sm among the entire spectrum of organisms throughout evolution from E. coli to humans. To achieve benign inapparent viral persistence, small DNA viruses are proposed to circumvent the host acute phase reaction (characterized by minimal inflammation) by mechanisms that are evoluti onarily adapted to the immune system and the related cytokine communic ation networks. A striking example of this is the relationship of hyme noptera to polydnaviruses, in which the virus is crucial to the recogn ition of self, development, and maintenance of genetic identity of bot h the host and virus. These observations in aggregate suggest that vir al replicons are not recent ''escapies'' of host replication, but rath er provide relentless pressure in driving the evolution of the host th rough cospeciation.