Temporal dynamics of koala retrovirus plasma RNA load in relation to faecal glucocorticoid metabolites and Chlamydia infection

Koala retrovirus (KoRV) is endemic throughout northern koala populations that are currently in steep decline. We have previously found a strong association between KoRV plasma RNA loads and the risk of secondary diseases, including chlamydiosis. However, it is unclear whether (1) KoRV loads are elevated in sick koalas due to the expansion of leucocyte populations; and/or (2) KoRV induces immunosuppression, increasing susceptibility to disease; and/or (3) KoRV and secondary diseases are related through a third variable such as the physiological stress response. Here, we assess the temporal dynamics of KoRV load over a year and, in relation to chlamydia, to explore the causal direction of their relationship. We also investigated co-variation in faecal glucocorticoid metabolites (FGMs: cortisol and corticosterone) with KoRV load and chlamydia. We found that KoRV load was stable within individuals over time. KoRV load did not increase in wild koalas when they began shedding Chlamydia pecorum or decrease when they then tested negative, through self-clearance or treatment. Koalas that were treated for chlamydiosis maintained higher KoRV loads than their healthy counterparts. We reveal that higher average KoRV loads are correlated with higher average FGM levels (R²=0.27), which could indicate that higher KoRV loads lead to higher stress levels or that higher cortisol levels increase KoRV replication through a glucocorticoid response element that we have identified in the KoRV genome. However, this association cannot explain the relationship between average KoRV load and chlamydia because average FGM levels were not significantly higher in koalas that contracted chlamydia or initially higher in those with chlamydial disease. Together, these results provide compelling evidence that KoRV load does not respond to a change in disease status and instead that koalas with consistently high KoRV loads are more likely to develop chlamydiosis, potentially through immunosuppression.