Infection-Induced Telomere Length Variation: Insights into Pathogenesis of Koala Retrovirus

Abstract

The pathogenesis of koala retrovirus (KoRV) has been explored in various contexts, yet its role in tumorigenesis remains incompletely understood. Unlike acute transforming retroviruses, KoRV lacks a viral oncogene but may contribute to oncogenesis via indirect mechanisms. However, the relationship between KoRV and telomere length, as a potential indicator of telomerase activity, has not been examined. This study investigates the effect of KoRV infection on telomere length in 47 samples from Southern Australian koalas in a novel telomere length quantification method. Telomere lengths of 30 KoRV-negative samples were compared to those of 17 KoRV-positive samples using the Absolute Human Telomere Length Quantification qPCR kit (ScienCell Research Laboratories, California, USA). The telomere length in KoRV-infected WBCs was significantly longer than the uninfected ones (t = -2.059, p-value = 0.045). In line with this, telomere length correlated positively with proviral load (r = 0.421, p-value = 0.003), further linking viral burden to telomere elongation. Furthermore, the effect of age on telomere length differed by infection status (β = -5329.7, p-value = 0.0038); KoRV-positive individuals exhibited longer telomeres at a younger age but experienced more rapid telomere attrition over time compared to KoRV-negative individuals. These results suggest KoRV promotes telomerase elongation ability and modulates age-related telomere dynamics, potentially contributing to subsequent cellular immortality and oncogenesis. These pathways may overlap with other retroviruses, where telomerase dysregulation contributes to their oncogenic potential. This study provides new insights into KoRV pathogenesis and DNA quantification methodology, which could be valuable for future research by identifying predictive markers for tumour progression and potential therapeutic targets in affected koalas.

Keywords: aging; cancer; koala retrovirus; oncogenesis; telomerase; telomere.

Figure 1

Comparison of telomere length in KoRV-infected (n = 17) and non-infected (n = 30) koalas. Infected animals showed a significantly higher telomere length based on the independent t-test (t = −2.059; p-value = 0.045). Error bars represent standard errors.

Figure 2

Scatter plot showing the relationship between KoRV proviral load (copies per 10³ β-actin copies) and total telomere length (Kb per diploid cell). Each point represents an individual sample. The solid line represents the regression estimate, and the shaded area represents the 95% confidence interval (CI) for the mean regression line (R² = 0.178). A significant positive correlation between the two variables was also detected by Pearson’s correlation analysis (r = 0.421, p-value = 0.003).

Figure 3

Scatter plot showing the relationship between age and total telomere length (Kb per diploid cell) with different KoRV infection status. Each point represents an individual sample. The solid lines represent the regression estimate, and the shaded areas represent the 95% confidence interval (CI) for the mean regression line. Negative values are shown as a result of the regression model’s extrapolation, due to sparse sampling at age extremes.