Differential and defective expression of Koala Retrovirus indicate complexity of host and virus evolution

Tarlinton, Rachael; Sarker, Nishat; Fabijan, Jessica; Dottorini, Tania; Woolford, Lucy; Meers, J.; Simmons, G. C.; Owen, Helen; Seddon, Jennifer M.; Hemmatzedah, Farhid; Trott, Darren J.; Speight, Natasha; Emes, Richard D.

doi:10.1101/211466

Cited by 19 publications

(26 citation statements)

References 76 publications

(134 reference statements)

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“…It was thought until recently that southern animals only possessed KoRV-A 14,23 and not other variants of the virus and this might be a potential explanation for the reduced disease burden in southern animals. However our recent work has shown that South Australian animals do in fact have multiple variants of KoRV (including KoRV-B) 16,38 . The previous lack of detection of non-KoRV-A variants in southern populations is likely due to the use of relatively insensitive end point PCR for detection, together with the overall low proviral and viral loads in these populations.…”

Section: Discussionmentioning

confidence: 99%

“…These studies determined prevalence based on the presence of the KoRV proviral pol gene 14,15 . In contrast, the transcriptomic analysis of QLD and SA koalas submandibular lymph node tissue demonstrated KoRV transcripts in 100% of animals from both populations 16 , although 27.6% SA koalas were missing transcripts of pol or env or both of these genes and had only truncated transcripts of the gag gene 16 . Given these complex findings, the role of KoRV in causing differences in disease occurrence between northern and southern populations is unlikely to be due only to proviral prevalence, and other viral characteristics must be explored.…”

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confidence: 90%

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

Sarker

Fabijan

Owen

et al. 2020

Sci Rep

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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...

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Section: Discussionmentioning

confidence: 99%

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confidence: 90%

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

Sarker

Fabijan

Owen

et al. 2020

Sci Rep

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“…Our understanding of the relationship between koalas and KoRV is rapidly evolving as a growing number of koalas are evaluated with increasingly sensitive methods. KoRV was originally thought to be spreading southwards after it was introduced to northern koala populations less than 200 years ago 41 , but recent analyses suggest it crossed into koalas up to 49,000 years ago 42 and a range of subtypes have been detected in both northern and southern koala populations 43 . 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 .…”

Section: Discussionmentioning

confidence: 99%

“…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 . Acknowledging that KoRV detection methods have different targets and sensitivities 43,46 , further study is clearly needed to tease out the complex interactions between this putative pathogen and its host.…”

Section: Discussionmentioning

confidence: 99%

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

Robbins

Hanger

Jelocnik

et al. 2020

Sci Rep

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Chlamydial disease control is increasingly utilised as a management tool to stabilise declining koala populations, and yet we have a limited understanding of the factors that contribute to disease progression. To examine the impact of host and pathogen genetics, we selected two geographically separated south east Queensland koala populations, differentially affected by chlamydial disease, and analysed koala major histocompatibility complex (MHC) genes, circulating strains of Chlamydia pecorum and koala retrovirus (KoRV) subtypes in longitudinally sampled, well-defined clinical groups. We found that koala immunogenetics and chlamydial genotypes differed between the populations. Disease progression was associated with specific MHC alleles, and we identified two putative susceptibility (DCb 03, DBb 04) and protective (DAb 10, UC 01:01) variants. Chlamydial genotypes belonging to both Multi-Locus Sequence Typing sequence type (ST) 69 and ompA genotype F were associated with disease progression, whereas ST 281 was associated with the absence of disease. We also detected different ompA genotypes, but not different STs, when long-term infections were monitored over time. By comparison, KoRV profiles were not significantly associated with disease progression. These findings suggest that chlamydial genotypes vary in pathogenicity and that koala immunogenetics and chlamydial strains are more directly involved in disease progression than KoRV subtypes.

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“…Yet, preservation of intact gag and env ORFs may indicate a functional importance, perhaps as restriction factors against exogenous KoRV. Moreover, some koala populations such as those located in Southern Australia (SA) are relatively resistant to KoRV induced disease and usually have low viral loads (Tarlinton et al, 2017). In contrast, koalas in northern Australia such as Queensland suffer from higher viremia and disease burden, and active KoRV infection is more prevalent.…”

Section: Endogenization In Real Time: Koala Retrovirusmentioning

confidence: 99%

Evolution of Immune Systems From Viruses and Transposable Elements

Broecker

Moelling

2019

Front. Microbiol.

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Virus-derived sequences and transposable elements constitute a substantial portion of many cellular genomes. Recent insights reveal the intimate evolutionary relationship between these sequences and various cellular immune pathways. At the most basic level, superinfection exclusion may be considered a prototypical virus-mediated immune system that has been described in both prokaryotes and eukaryotes. More complex immune mechanisms fully or partially derived from mobile genetic elements include CRISPR-Cas of prokaryotes and the RAG1/2 system of vertebrates, which provide immunological memory of foreign genetic elements and generate antibody and T cell receptor diversity, respectively. In this review, we summarize the current knowledge on the contribution of mobile genetic elements to the evolution of cellular immune pathways. A picture is emerging in which the various cellular immune systems originate from and are spread by viruses and transposable elements. Immune systems likely evolved from simple superinfection exclusion to highly complex defense strategies.

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Differential and defective expression of Koala Retrovirus indicate complexity of host and virus evolution

Cited by 19 publications

References 76 publications

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

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

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

Evolution of Immune Systems From Viruses and Transposable Elements

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