Koala retrovirus viral load and disease burden in distinct northern and southern koala populations

Abstract

Koala retrovirus (KoRV) displays features of both an endogenous and exogenous virus and is linked to neoplasia and immunosuppression in koalas. This study explores the apparent differences in the nature and impact of KoRV infection between geographically and genetically separated "northern" and "southern" koala populations, by investigating the disease status, completeness of the KoRV genome and the proviral (DNA) and viral (RNA) loads of 71 northern and 97 southern koalas. All northern animals were positive for all KoRV genes (gag, pro-pol and env) in both DNA and RNA forms, whereas many southern animals were missing one or more KoRV genes. There was a significant relationship between the completeness of the KoRV genome and clinical status in this population. The proviral and viral loads of the northern population were significantly higher than those of the southern population (P < 0.0001), and many provirus-positive southern animals failed to express any detectable KoRV RNA. Across both populations there was a positive association between proviral load and neoplasia (p = 0.009). Potential reasons for the differences in the nature of KoRV infection between the two populations are discussed. Koala retrovirus (KoRV) was first identified in tissues from a leukemic koala in 1988 1 and the full genome sequence was published in 2000 2. This is a unique endogenous retrovirus which is also capable of being transmitted horizontally 3. It is thought that KoRV plays a role in the pathogenesis of lymphoid neoplasia as well as causing immunosuppression, making koalas more susceptible to developing overt chlamydial disease 4 , which is a major threat to koala populations. However while there appears to be a strong association between KoRV infection and these diseases in koalas, there is currently little if any published data proving a causal link 3,5,6. Anecdotally, there are differences in disease prevalence between koala populations in northern and southern Australia. The prevalence of lymphoid neoplasia is high in northern koalas 7 compared to southern koalas where lymphosarcoma has only recently been reported 8. The prevalence of Chlamydia pecorum infection and overt chlamydial disease is also high in northern koalas in comparison to southern populations, with chlamydial disease reported in 52% of more than 20,000 koala admissions to wildlife hospitals in South East Queensland (SE QLD) 9. In contrast, a recent necropsy study in South Australia (SA) reported only 21% of koalas with clinically overt disease 10. Conversely, SA kocalas have a higher prevalence of oxalate nephrosis than QLD koalas, with 55% of SA koalas demonstrating renal dysfunction due to oxalate nephrosis 11. These differences in disease prevalence may be the result of genetic differences between northern southern koala populations 12. Animals in the southern part of the range (the states of Victoria, South Australia [SA] and southern New South Wales [NSW]) have undergone a severe genetic bottleneck as a result of hunting pressures in the late 1800's. Thes...

Koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (Phascolarctos cinereus): a review

“…The prevalence of KoRV varies depending on the geographical location of a particular population [ 13 ]. Variations in KoRV proviral loads in koala genomes have been reported by us and others [ 5 , 13 , 16 , 23 – 25 ]. These reports are indicative of the ongoing endogenization process that KoRV is undergoing.…”

“…KoRV is now endemic in both wild and captive koalas and represents a major threat to koala health [ 7 , 9 , 23 , 31 – 33 ]. KoRV shows variations in its prevalence depending on the geographical location of the population and the virus subtype [ 13 , 25 , 33 – 35 ] (Fig. 1 ).…”

“…Within the northern population, the prevalence of KoRV provirus is regarded as 100%, with every reported case of testing yielding positive evidence of the presence of a provirus [ 4 , 9 , 13 , 33 ] (Table 2 ). The southern population previously showed a much lower prevalence, reportedly ranging from 14.8 to 25% [ 8 , 13 , 34 ]; however, the three most recent studies have shown markedly higher figures, ranging from 42.4 to 99.0% [ 25 , 33 , 35 ] (Table 2 ).…”

Koala immunogenetics and chlamydial strain type are more directly involved in chlamydial disease progression in koalas from two south east Queensland koala populations than koala retrovirus subtypes

“…Consistent with these analyses, we found a strikingly similar prevalence of KoRV subtypes at each of our study sites, suggesting that the spread of KoRV in this region occurred before gene flow between our populations was limited by the BVB 24 and the rapid and widespread declines in koala populations 30,000-40,000 years ago 23 . Utilising deep sequencing of the KoRV proviral env gene and our well-defined clinical groups, we failed to detect any association between the proviral detection of any KoRV subtype, including KoRV-B 15 , and disease progression 16,44,45 . This suggests that the presence of KoRV provirus alone is not sufficient to influence chlamydial disease progression and that subtype expression might be more important 46 .…”

Koala Retrovirus Diversity, Transmissibility, and Disease Associations

“…The complete koala genome was not available at the time of our study for identifying primers for pVL normalization with single copy genes. Fourthly, as with other molecular epidemiologic studies using PCR, our results could include detection of defective genomes and may not reflect infectivity of the detected variants (7,16,20,46). Finally, as koalas are infected with multiple subtypes, determination of the contributions of a single or multiple KoRV variants to neoplasia or other diseases is complex and requires research beyond the scope of our study, including animal model studies with infectious molecular clones.…”