Evolutionary aspects of oncogenic herpesviruses

Abstract

Several of the gamma-herpesviruses are known to have cellular transforming and oncogenic properties. The genomes of eight distinct gamma-herpesviruses have been sequenced, and the resulting database of information has enabled the identification of genetic similarities and differences between evolutionarily closely related and distant viruses of the subfamily and between the gamma-herpesviruses and other members of the herpesvirus family. The recognition of coincident loci of genetic divergence between individual gamma-herpesviruses and the identification of novel genes and cellular gene homologues in these genomic regions has delineated a subset of genes that are likely to contribute to the unique biological properties of these viruses. These genes, together with gamma-herpesvirus conserved genes not found in viruses outside the family, might be responsible for virus specific pathogenicity and pathogenic effects, such as viral associated neoplasia, characteristic of the subfamily. The presence of the gamma-herpesvirus major divergent genomic loci and the apparent increased mutational frequencies of homologous genes (where they occur) within these regions, indicates that these loci possess particular features that drive genetic divergence. Whatever the mechanisms underlying this phenomenon, it potentially provides the basis for the relatively rapid adaptation and evolution of gamma-herpesviruses and the diversity of biological and pathogenic properties.

Figure 1

Alignment of the genomes of the sequenced γ-herpesviruses. Conserved homologous genes, non-conserved genes, and “unique” (shared by no more than two viruses) genes are indicated by shaded, hatched, and open arrows, respectively. Conserved gene blocks are shown by the boxes labelled I to IV, with intervening and flanking γ-herpesvirus divergent loci (γDL-A to γDL-D), divergent between multiple γ-herpesviruses, indicated by shading. Where possible, the homologous genes within the DL regions are adjoined by broken lines. The interferon regulatory factor (IRF) loci, found only in HHV-8 and RRV, disrupt conserved gene block IV. Terminal repeats, internal repeats and known or suspected replication origins are indicated by open boxes, filled boxes (or arrows), and circles, respectively. AHV-1, alcelaphine herpesvirus 1; EBV, Epstein-Barr virus; EHV-2, equine herpesvirus 2; HHV-8, human herpesvirus 8; HVA, herpesvirus ateles; HVS, herpesvirus saimiri; MHV-68, murine herpesvirus 68; RRV, rhesus rhadinovirus.