Inherited proviruses, or endogenous retroviruses (ERVs), are inherited in Mendelian fashion, and thus can provide a 'fossil record' for vertebrate infection by retroviruses [2]. Individual integration events can be distinguished by the cellular sequences flanking the provirus, outside the long terminal repeats (LTRs) that characterize each provirus; for example, a provirus at a common site in two related species implies an insertion event pre-dating the evolutionary split between the species. Studies of primate ERVs indicate an ongoing process of retrovirus acquisition for a period in excess of 30 million years [3]. Analysis of the human genome sequence reveals the presence of between 30 and 40 phylogenetic groups of viruses, ranging in prevalence from 1 copy to more than 1,000. Each group is thought to descend from one cross-species infection, followed by a series of amplification events, most probably including re-infection [4]. Indeed, it appears that proviruses make up a greater fraction of the human genome (6 to 8%) than do protein-coding sequences (1 to 2%) [5]. Only a minute fraction of the inherited proviruses can encode functional retroviruses, as all have suffered mutational decay to an extent related to their period of residence in the genome. Nevertheless, ERVs are associated with a wide range of biological phenomena, including neoplasia. The replication properties of retro-viruses and the structures and distribution of proviruses in the germline allow us to infer the likely course of events during a wave of endogenization, but until now the process has not lent itself to experimental study [2]. The ongoing infection of koalas presents an opportunity to remedy that situation.
KoRV was originally described as an endogenous retrovirus based on its ubiquitous presence in all koala samples initially examined [6]. However, unlike most ERVs, KoRV appeared biologically active with ready demonstration of viral particles from cultured koala lymphocytes [6] and significant variation of KoRV copy number [7]. These observations prompted Tarlington et al. [1] to investigate the distribution and properties of KoRV in more detail. On the one hand, consistent with the proposition that KoRVs are endogenous, they could show the presence of viral sequences in sperm by fluorescent in situ hybridization and demonstrate Mendelian inheritance of specific proviruses in related individuals by Southern hybridization. On the other hand, variation in the KoRV envelope gene sequence was consistent with the propagation of exogenous KoRV. Furthermore, there was considerable variation in the proviral content of unrelated animals, implying that these elements had not been present in the germline for sufficient time to allow genetic fixation.
Studies of koala samples from different geographic locations suggest an on-going process of endogenization spreading from the north of Australia, where all animals contain endogenous KoRV, to the south, where some animals are still virus-free. Setting an accurate time for the start of this epidemic remains a problem; on the basis of the similarity of KoRV to an exogenous virus (one that is not integrated into the germline), called Gibbon Ape Leukemia Virus (GALV), Tarlington et al. [1] conclude that it occurred less than 100 years ago. However, this may be an underestimate given the difficulties of determining rates of retrovirus evolution [8]. PCR examination of preserved koala DNA, if any suitable specimens can be identified, might provide a means of addressing this question.