Geographic patterns of koala retrovirus genetic diversity, endogenization and subtype distributions

Abstract

Koala retrovirus subtype A is the youngest endogenized retrovirus, providing a unique system to elucidate retroviral-host co-evolution. We characterised KoRV geography using faecal DNA from 192 samples across 20 populations throughout the koalas range. We reveal an abrupt change in KoRV genetics and incidence at the Victoria/NSW state border. In northern koalas, pol gene copies were ubiquitously present at greater than 5 per-cell, consistent with endogenous KoRV. In southern koalas, pol copies were detected in only 25.8% of koalas and always at copy numbers less than one, while the env gene was detected in all animals and in a majority at copy numbers of greater than one per-cell. These results suggest that southern koalas carry partial endogenous KoRV-like sequences. Deep sequencing of the env hypervariable region revealed three putatively endogenous KoRV-A sequences in northern koalas and a single, distinct sequence present in all southern koalas. Among northern populations, env sequence diversity decreased with distance from the equator, suggesting infectious KoRV-A invaded the koala genome in northern Australia and then spread south. The previously described exogenous KoRV subtypes (B-K), two novel subtypes (L and M), and intermediate or hybrid subtypes were detected in all northern koala populations but strikingly absent from all southern animals tested. Apart from KoRV-D, these exogenous subtypes were generally locally prevalent but geographically restricted, producing KoRV genetic differentiation among northern populations. This suggests that sporadic evolution and local transmission of the exogenous subtypes has occurred within northern Australia, but this has not extended into animals within southern Australia. Author SummaryRetrovirus infection is generally synonymous with disease; however, retroviruses can also become endogenous (incorporated into the germline) and thereby directly contribute to the genetic makeup of a species. This has occurred in all vertebrates, yet little is known about the endogenization process. As the youngest virus known to be endogenized, koala retrovirus (KoRV) offers a unique opportunity to study these early stages of co-evolution. This study reveals a comprehensive picture of KoRV biogeography that informs our understanding of how host population history, host suppression and transmission dynamics can influence retroviral evolution. KoRV is also associated with chlamydiosis and neoplasia in the vulnerable koala. Our improved understanding of how KoRV variants are distributed should guide conservation management to help limit disease.