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Автор: Grafiati

Опубліковано: 10 грудня 2022

Оновлено: 28 січня 2023

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1

Hanger, Jon J., Lindell D. Bromham, Jeff J. McKee, Tracy M. O'Brien, and Wayne F. Robinson. "The Nucleotide Sequence of Koala (Phascolarctos cinereus) Retrovirus: a Novel Type C Endogenous Virus Related to Gibbon Ape Leukemia Virus." Journal of Virology 74, no. 9 (May 1, 2000): 4264–72. http://dx.doi.org/10.1128/jvi.74.9.4264-4272.2000.

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ABSTRACT A novel retrovirus, morphologically consistent with mammalian C-type retroviruses, was detected by electron microscopy in mitogen-stimulated peripheral blood mononuclear cell cultures from 163 koalas and in lymphoma tissue from 3 koalas. PCR amplified provirus from the blood and tissues of 17 wild and captive koalas, and reverse transcriptase-PCR demonstrated viral mRNA, viral genomic RNA, and reverse transcriptase activity in koala serum and cell culture supernatants. Comparison of viral sequences derived from genomic DNA and mRNA showed identity indicative of a single retroviral species—here designated koala retrovirus (KoRV). Southern blot analysis of koala tissue genomic DNA using labelled KoRV probes demonstrated banding consistent with an endogenous retrovirus. Complete and apparently truncated proviruses were detected in DNA of both clinically normal koalas and those with hematopoietic disease. KoRV-related viruses were not detected in other marsupials, and phylogenetic analysis showed that KoRV paradoxically clusters with gibbon ape leukemia virus (GALV). The strong similarity between GALV and KoRV suggests that these viruses are closely related and that recent cross-host transmission has occurred. The complete proviral DNA sequence of KoRV is reported.

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2

Stephenson, Tamsyn, Natasha Speight, Wai Yee Low, Lucy Woolford, Rick Tearle, and Farhid Hemmatzadeh. "Molecular Diagnosis of Koala Retrovirus (KoRV) in South Australian Koalas (Phascolarctos cinereus)." Animals 11, no. 5 (May 20, 2021): 1477. http://dx.doi.org/10.3390/ani11051477.

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Koala retrovirus, a recent discovery in Australian koalas, is endogenised in 100% of northern koalas but has lower prevalence in southern populations, with lower proviral and viral loads, and an undetermined level of endogenisation. KoRV has been associated with lymphoid neoplasia, e.g., lymphoma. Recent studies have revealed high complexity in southern koala retroviral infections, with a need to clarify what constitutes positive and negative cases. This study aimed to define KoRV infection status in Mount Lofty Ranges koalas in South Australia using RNA-seq and proviral analysis (n = 216). The basis for positivity of KoRV was deemed the presence of central regions of the KoRV genome (gag 2, pol, env 1, and env 2) and based on this, 41% (89/216) koalas were positive, 57% (124/216) negative, and 2% inconclusive. These genes showed higher expression in lymph node tissue from KoRV positive koalas with lymphoma compared with other KoRV positive koalas, which showed lower, fragmented expression. Terminal regions (LTRs, partial gag, and partial env) were present in SA koalas regardless of KoRV status, with almost all (99.5%, 215/216) koalas positive for gag 1 by proviral PCR. Further investigation is needed to understand the differences in KoRV infection in southern koala populations.

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3

Löber, Ulrike, Matthew Hobbs, Anisha Dayaram, Kyriakos Tsangaras, Kiersten Jones, David E. Alquezar-Planas, Yasuko Ishida, et al. "Degradation and remobilization of endogenous retroviruses by recombination during the earliest stages of a germ-line invasion." Proceedings of the National Academy of Sciences 115, no. 34 (August 6, 2018): 8609–14. http://dx.doi.org/10.1073/pnas.1807598115.

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Endogenous retroviruses (ERVs) are proviral sequences that result from colonization of the host germ line by exogenous retroviruses. The majority of ERVs represent defective retroviral copies. However, for most ERVs, endogenization occurred millions of years ago, obscuring the stages by which ERVs become defective and the changes in both virus and host important to the process. The koala retrovirus, KoRV, only recently began invading the germ line of the koala (Phascolarctos cinereus), permitting analysis of retroviral endogenization on a prospective basis. Here, we report that recombination with host genomic elements disrupts retroviruses during the earliest stages of germ-line invasion. One type of recombinant, designated recKoRV1, was formed by recombination of KoRV with an older degraded retroelement. Many genomic copies of recKoRV1 were detected across koalas. The prevalence of recKoRV1 was higher in northern than in southern Australian koalas, as is the case for KoRV, with differences in recKoRV1 prevalence, but not KoRV prevalence, between inland and coastal New South Wales. At least 15 additional different recombination events between KoRV and the older endogenous retroelement generated distinct recKoRVs with different geographic distributions. All of the identified recombinant viruses appear to have arisen independently and have highly disrupted ORFs, which suggests that recombination with existing degraded endogenous retroelements may be a means by which replication-competent ERVs that enter the germ line are degraded.

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4

Oliveira, Nidia M., Karen B. Farrell, and Maribeth V. Eiden. "In Vitro Characterization of a Koala Retrovirus." Journal of Virology 80, no. 6 (March 15, 2006): 3104–7. http://dx.doi.org/10.1128/jvi.80.6.3104-3107.2006.

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ABSTRACT Recently, a new endogenous koala gammaretrovirus, designated KoRV, was isolated from koalas. The KoRV genome shares 78% nucleotide identity with another gammaretrovirus, gibbon ape leukemia virus (GALV). KoRV is endogenous in koalas, while GALV is exogenous, suggesting that KoRV predates GALV and that gibbons and koalas acquired the virus at different times from a common source. We have determined that subtle adaptive differences between the KoRV and GALV envelope genes account for differences in their receptor utilization properties. KoRV represents a unique example of a gammaretrovirus whose envelope has evolved to allow for its expanded host range and zoonotic potential.

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5

Quigley, Bonnie L., and Peter Timms. "Helping koalas battle disease – Recent advances in Chlamydia and koala retrovirus (KoRV) disease understanding and treatment in koalas." FEMS Microbiology Reviews 44, no. 5 (June 18, 2020): 583–605. http://dx.doi.org/10.1093/femsre/fuaa024.

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ABSTRACT The iconic Australian marsupial, the koala (Phascolarctos cinereus), has suffered dramatic population declines as a result of habitat loss and fragmentation, disease, vehicle collision mortality, dog attacks, bushfires and climate change. In 2012, koalas were officially declared vulnerable by the Australian government and listed as a threatened species. In response, research into diseases affecting koalas has expanded rapidly. The two major pathogens affecting koalas are Chlamydia pecorum, leading to chlamydial disease and koala retrovirus (KoRV). In the last eight years, these pathogens and their diseases have received focused study regarding their sources, genetics, prevalence, disease presentation and transmission. This has led to vast improvements in pathogen detection and treatment, including the ongoing development of vaccines for each as a management and control strategy. This review will summarize and highlight the important advances made in understanding and combating C. pecorum and KoRV in koalas, since they were declared a threatened species. With complementary advances having also been made from the koala genome sequence and in our understanding of the koala immune system, we are primed to make a significant positive impact on koala health into the future.

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6

Higgins, Damien P., Quintin Lau, and Iona Maher. "Koala immunology and the koala retrovirus (KoRV)." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 35–38. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1611.

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7

Joyce, Briony A., Michaela D. J. Blyton, Stephen D. Johnston, Paul R. Young, and Keith J. Chappell. "Koala retrovirus genetic diversity and transmission dynamics within captive koala populations." Proceedings of the National Academy of Sciences 118, no. 38 (September 7, 2021): e2024021118. http://dx.doi.org/10.1073/pnas.2024021118.

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Koala populations are currently in rapid decline across Australia, with infectious diseases being a contributing cause. The koala retrovirus (KoRV) is a gammaretrovirus present in both captive and wild koala colonies that presents an additional challenge for koala conservation in addition to habitat loss, climate change, and other factors. Currently, nine different subtypes (A to I) have been identified; however, KoRV genetic diversity analyses have been limited. KoRV is thought to be exogenously transmitted between individuals, with KoRV-A also being endogenous and transmitted through the germline. The mechanisms of exogenous KoRV transmission are yet to be extensively investigated. Here, deep sequencing was employed on 109 captive koalas of known pedigree, housed in two institutions from Southeast Queensland, to provide a detailed analysis of KoRV transmission dynamics and genetic diversity. The final dataset included 421 unique KoRV sequences, along with the finding of an additional subtype (KoRV-K). Our analysis suggests that exogenous transmission of KoRV occurs primarily between dam and joey, with evidence provided for multiple subtypes, including nonendogenized KoRV-A. No evidence of sexual transmission was observed, with mating partners found to share a similar number of sequences as unrelated koala pairs. Importantly, both distinct captive colonies showed similar trends. These findings indicate that breeding strategies or antiretroviral treatment of females could be employed as effective management approaches in combating KoRV transmission.

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8

Kinney, Matthew E., and Geoffrey W. Pye. "KOALA RETROVIRUS: A REVIEW." Journal of Zoo and Wildlife Medicine 47, no. 2 (June 2016): 387–96. http://dx.doi.org/10.1638/2015-0185.1.

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9

Kayesh, Mohammad Enamul Hoque, Md Abul Hashem, and Kyoko Tsukiyama-Kohara. "Toll-Like Receptor Expression Profiles in Koala (Phascolarctos cinereus) Peripheral Blood Mononuclear Cells Infected with Multiple KoRV Subtypes." Animals 11, no. 4 (April 1, 2021): 983. http://dx.doi.org/10.3390/ani11040983.

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Toll-like receptors (TLRs), evolutionarily conserved pattern recognition receptors, play an important role in innate immunity by recognizing microbial pathogen-associated molecular patterns. Koala retrovirus (KoRV), a major koala pathogen, exists in both endogenous (KoRV-A) and exogenous forms (KoRV-B to J). However, the expression profile of TLRs in koalas infected with KoRV-A and other subtypes is yet to characterize. Here, we investigated TLR expression profiles in koalas with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C). To this end, we cloned partial sequences for TLRs (TLR2–10 and TLR13), developed real-time PCR assays, and determined TLRs mRNA expression patterns in koala PBMCs and/or tissues. All the reported TLRs for koala were expressed in PBMCs, and variations in TLR expression were observed in koalas infected with exogenous subtypes (KoRV-B and KoRV-C) compared to the endogenous subtype (KoRV-A) only, which indicates the implications of TLRs in KoRV infection. TLRs were also found to be differentially expressed in koala tissues. This is the first report of TLR expression profiles in koala, which provides insights into koala’s immune response to KoRV infection that could be utilized for the future exploitation of TLR modulators in the maintenance of koala health.

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10

Cui, Pin, Ulrike Löber, David E. Alquezar-Planas, Yasuko Ishida, Alexandre Courtiol, Peter Timms, Rebecca N. Johnson, et al. "Comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome." PeerJ 4 (March 28, 2016): e1847. http://dx.doi.org/10.7717/peerj.1847.

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Background.Retroviral integration into the host germline results in permanent viral colonization of vertebrate genomes. The koala retrovirus (KoRV) is currently invading the germline of the koala (Phascolarctos cinereus) and provides a unique opportunity for studying retroviral endogenization. Previous analysis of KoRV integration patterns in modern koalas demonstrate that they share integration sites primarily if they are related, indicating that the process is currently driven by vertical transmission rather than infection. However, due to methodological challenges, KoRV integrations have not been comprehensively characterized.Results.To overcome these challenges, we applied and compared three target enrichment techniques coupled with next generation sequencing (NGS) and a newly customized sequence-clustering based computational pipeline to determine the integration sites for 10 museum Queensland and New South Wales (NSW) koala samples collected between the 1870s and late 1980s. A secondary aim of this study sought to identify common integration sites across modern and historical specimens by comparing our dataset to previously published studies. Several million sequences were processed, and the KoRV integration sites in each koala were characterized.Conclusions.Although the three enrichment methods each exhibited bias in integration site retrieval, a combination of two methods, Primer Extension Capture and hybridization capture is recommended for future studies on historical samples. Moreover, identification of integration sites shows that the proportion of integration sites shared between any two koalas is quite small.

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11

Wedrowicz, Faye, Jennifer Mosse, Wendy Wright, and Fiona E. Hogan. "Using non-invasive sampling methods to determine the prevalence and distribution of Chlamydia pecorum and koala retrovirus in a remnant koala population with conservation importance." Wildlife Research 45, no. 4 (2018): 366. http://dx.doi.org/10.1071/wr17184.

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Context Pathogenic infections are an important consideration for the conservation of native species, but obtaining such data from wild populations can be expensive and difficult. Two pathogens have been implicated in the decline of some koala (Phascolarctos cinereus) populations: urogenital infection with Chlamydia pecorum and koala retrovirus subgroup A (KoRV-A). Pathogen data for a wild koala population of conservation importance in South Gippsland, Victoria are essentially absent. Aims This study uses non-invasive sampling of koala scats to provide prevalence and genotype data for C. pecorum and KoRV-A in the South Gippsland koala population, and compares pathogen prevalence between wild koalas and koalas in rescue shelters. Methods C. pecorum and KoRV-A provirus were detected by PCR of DNA isolated from scats collected in the field. Pathogen genetic variation was investigated using DNA sequencing of the C. pecorum ompA and KoRV-A env genes. Key results C. pecorum and KoRV-A were detected in 61% and 27% of wild South Gippsland individuals tested, respectively. KoRV-A infection tended to be higher in shelter koalas compared with wild koalas. In contrast with other Victorian koala populations sampled, greater pathogen diversity was present in South Gippsland. Conclusions In the South Gippsland koala population, C. pecorum is widespread and common whereas KoRV appears less prevalent than previously thought. Further work exploring the dynamics of these pathogens in South Gippsland koalas is warranted and may help inform future conservation strategies for this important population. Implications Non-invasive genetic sampling from scats is a powerful method for obtaining data regarding pathogen prevalence and diversity in wildlife. The use of non-invasive methods for the study of pathogens may help fill research gaps in a way that would be difficult or expensive to achieve using traditional methods.

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12

Denner, Joachim. "Vaccination against the Koala Retrovirus (KoRV): Problems and Strategies." Animals 11, no. 12 (December 14, 2021): 3555. http://dx.doi.org/10.3390/ani11123555.

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The koala retrovirus (KoRV) is spreading in the koala population from the north to the south of Australia and is also in the process of endogenization into the koala genome. Virus infection is associated with tumorigenesis and immunodeficiency and is contributing to the decline of the animal population. Antibody production is an excellent marker of retrovirus infection; however, animals carrying endogenous KoRV are tolerant. Therefore, the therapeutic immunization of animals carrying endogenous KoRV seems to be ineffective. Using the recombinant transmembrane (TM) envelope protein of the KoRV, we immunized goats, rats and mice, obtaining in all cases neutralizing antibodies which recognize epitopes in the fusion peptide proximal region (FPPR), and in the membrane-proximal external region (MPER). Immunizing several animal species with the corresponding TM envelope protein of the closely related porcine endogenous retrovirus (PERV), as well as the feline leukemia virus (FeLV), we also induced neutralizing antibodies with similar epitopes. Immunizing with the TM envelope protein in addition to the surface envelope proteins of all three viruses resulted in higher titers of neutralizing antibodies. Immunizing KoRV-negative koalas with our vaccine (which is composed of both envelope proteins) may protect these animals from infection, and these may be the starting points of a virus-free population.

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13

Kayesh, Mohammad Enamul Hoque, Md Abul Hashem, Fumie Maetani, Atsushi Goto, Noriko Nagata, Aki Kasori, Tetsuya Imanishi, and Kyoko Tsukiyama-Kohara. "Molecular Insights into Innate Immune Response in Captive Koala Peripheral Blood Mononuclear Cells Co-Infected with Multiple Koala Retrovirus Subtypes." Pathogens 11, no. 8 (August 14, 2022): 911. http://dx.doi.org/10.3390/pathogens11080911.

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Koala retrovirus (KoRV) exists in both endogenous and exogenous forms and has appeared as a major threat to koala health and conservation. Currently, there are twelve identified KoRV subtypes: an endogenous subtype (KoRV-A) and eleven exogenous subtypes (KoRV-B to -I, KoRV-K, -L, and -M). However, information about subtype-related immune responses in koalas against multiple KoRV infections is limited. In this study, we investigated KoRV-subtype (A, B, C, D, and F)-related immunophenotypic changes, including CD4, CD8b, IFN-γ, IL-6, and IL-10 mRNA expression, in peripheral blood mononuclear cells (PBMCs) obtained from captive koalas (n = 37) infected with multiple KoRV subtypes (KoRV-A to F) reared in seven Japanese zoos. Based on KoRV subtype infection profiles, no significant difference in CD4 and CD8b mRNA expression was observed in the study populations. Based on the different KoRV subtype infections, we found that the IFN-γ mRNA expression in koala PMBCs differs insignificantly (p = 0.0534). In addition, IL-6 and IL-10 mRNA expression also did not vary significantly in koala PBMCs based on KoRV subtype differences. We also investigated the Toll-like receptors (TLRs) response, including TLR2–10, and TLR13 mRNA in koala PBMCs infected with multiple KoRV subtypes. Significant differential expression of TLR5, 7, 9, 10, and 13 mRNA was observed in the PBMCs from koalas infected with different KoRV subtypes. Therefore, based on the findings of this study, it is assumed that co-infection of multiple KoRV subtypes might modify the host innate immune response, including IFN-γ and TLRs responses. However, to have a more clear understanding regarding the effect of multiple KoRV subtypes on host cytokines and TLR response and pathogenesis, further large-scale studies including the koalas negative for KoRV and koalas infected with other KoRV subtypes (KoRV-A to -I, KoRV-K, -L and -M) are required.

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14

Simmons, Greg, Paul Young, Jeff McKee, Joanne Meers, and Tetsuo MIZUNO. "The Epidemiology of Koala Retrovirus." Journal of Veterinary Epidemiology 15, no. 1 (2011): 1–9. http://dx.doi.org/10.2743/jve.15.1.

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15

Shimode, Sayumi, So Nakagawa, Rokusuke Yoshikawa, Takayuki Shojima, and Takayuki Miyazawa. "Heterogeneity of koala retrovirus isolates." FEBS Letters 588, no. 1 (November 12, 2013): 41–46. http://dx.doi.org/10.1016/j.febslet.2013.10.046.

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16

Tarlinton, Rachael, Joanne Meers, Jon Hanger, and Paul Young. "Real-time reverse transcriptase PCR for the endogenous koala retrovirus reveals an association between plasma viral load and neoplastic disease in koalas." Journal of General Virology 86, no. 3 (March 1, 2005): 783–87. http://dx.doi.org/10.1099/vir.0.80547-0.

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Koala retrovirus (KoRV) is a newly described endogenous retrovirus and is unusual in that inserts comprise a full-length replication competent genome. As koalas are known to suffer from an extremely high incidence of leukaemia/lymphoma, the association between this retrovirus and disease in koalas was examined. Using quantitative real-time reverse transcriptase PCR it was demonstrated that KoRV RNA levels in plasma are significantly increased in animals suffering from leukaemia or lymphoma when compared with healthy animals. Increased levels of KoRV were also seen for animals with clinical chlamydiosis. A significant positive association between viral RNA levels and age was also demonstrated. Real-time PCR demonstrated as much as 5 log variation in KoRV proviral DNA levels in genomic DNA extracted from whole blood from different animals. Taken together these data indicate that KoRV is an active endogenous retrovirus and suggests that it may be causally linked to neoplastic disease in koalas.

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17

Cui, Jie, Gilda Tachedjian, Mary Tachedjian, Edward C. Holmes, Shuyi Zhang, and Lin-Fa Wang. "Identification of diverse groups of endogenous gammaretroviruses in mega- and microbats." Journal of General Virology 93, no. 9 (September 1, 2012): 2037–45. http://dx.doi.org/10.1099/vir.0.043760-0.

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A previous phylogenetic study suggested that mammalian gammaretroviruses may have originated in bats. Here we report the discovery of RNA transcripts from two putative endogenous gammaretroviruses in frugivorous (Rousettus leschenaultii retrovirus, RlRV) and insectivorous (Megaderma lyra retrovirus, MlRV) bat species. Both genomes possess a large deletion in pol, indicating that they are defective retroviruses. Phylogenetic analysis places RlRV and MlRV within the diversity of mammalian gammaretroviruses, with the former falling closer to porcine endogenous retroviruses and the latter to Mus dunni endogenous virus, koala retrovirus and gibbon ape leukemia virus. Additional genomic mining suggests that both microbat (Myotis lucifugus) and megabat (Pteropus vampyrus) genomes harbour many copies of endogenous retroviral forms related to RlRV and MlRV. Furthermore, phylogenetic analysis reveals the presence of three genetically diverse groups of endogenous gammaretroviruses in bat genomes, with M. lucifugus possessing members of all three groups. Taken together, this study indicates that bats harbour distinct gammaretroviruses and may have played an important role as reservoir hosts during the diversification of mammalian gammaretroviruses.

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18

Young, Paul R. "Koala retrovirus (KoRV) and its variants." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 59–60. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1617.

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19

Blyton, Michaela D. J., Michael Pyne, Paul Young, and Keith Chappell. "Koala retrovirus load and non-A subtypes are associated with secondary disease among wild northern koalas." PLOS Pathogens 18, no. 5 (May 19, 2022): e1010513. http://dx.doi.org/10.1371/journal.ppat.1010513.

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Koala Retrovirus (KoRV) has been associated with neoplasia in the vulnerable koala (Phascolarctos cinereus). However, there are conflicting findings regarding its association with secondary disease. We undertook a large-scale assessment of how the different KoRV subtypes and viral load are associated with Chlamydia pecorum infection and a range of disease pathologies in 151 wild koalas admitted for care to Currumbin Wildlife Hospital, Australia. Viral load (KoRV pol copies per ml of plasma) was the best predictor of more disease pathologies than any other KoRV variable. The predicted probability of a koala having disease symptoms increased from 25% to over 85% across the observed range of KoRV load, while the predicted probability of C. pecorum infection increased from 40% to over 80%. We found a negative correlation between the proportion of env deep sequencing reads that were endogenous KoRV-A and total KoRV load. This is consistent with suppression of endogenous KoRV-A, while the exogenous KoRV subtypes obtain high infection levels. Additionally, we reveal evidence that the exogenous subtypes are directly associated with secondary disease, with the proportion of reads that were the endogenous KoRV-A sequence a negative predictor of overall disease probability after the effect of KoRV load was accounted for. Further, koalas that were positive for KoRV-D or KoRV-D/F were more likely to have urogenital C. pecorum infection or low body condition score, respectively, irrespective of KoRV load. By contrast, our findings do not support previous findings that KoRV-B in particular is associated with Chlamydial disease. Based on these findings we suggest that koala research and conservation programs should target understanding what drives individual differences in KoRV load and limiting exogenous subtype diversity within populations, rather than seeking to eliminate any particular subtype.

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20

Hanger, Jon J., and Jo Loader. "Disease in wild koalas (Phascolarctos cinereus) with possible koala retrovirus involvement." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 19–29. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1609.

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21

Mulot, Baptiste. "Koala retrovirus related diseases in European zoo-based koalas (Phascolarctos cinereus)." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 51–54. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1614.

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22

Kayesh, Mohammad Enamul Hoque, Osamu Yamato, Mohammad Mahbubur Rahman, Md Abul Hashem, Fumie Maetani, Taiki Eiei, Kyoya Mochizuki, Hiroko Sakurai, and Kyoko Tsukiyama-Kohara. "Molecular dynamics of koala retrovirus infection in captive koalas in Japan." Archives of Virology 164, no. 3 (January 17, 2019): 757–65. http://dx.doi.org/10.1007/s00705-019-04149-5.

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23

Kayesh, Mohammad Enamul Hoque, Md Abul Hashem, Fumie Maetani, Taiki Eiei, Kyoya Mochizuki, Shinsaku Ochiai, Ayaka Ito, et al. "CD4, CD8b, and Cytokines Expression Profiles in Peripheral Blood Mononuclear Cells Infected with Different Subtypes of KoRV from Koalas (Phascolarctos cinereus) in a Japanese Zoo." Viruses 12, no. 12 (December 9, 2020): 1415. http://dx.doi.org/10.3390/v12121415.

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Koala retrovirus (KoRV) poses a major threat to koala health and conservation, and currently has 10 identified subtypes: an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). However, subtype-related variations in koala immune response to KoRV are uncharacterized. In this study, we investigated KoRV-related immunophenotypic changes in a captive koala population (Hirakawa zoo, Japan) with a range of subtype infection profiles (KoRV-A only vs. KoRV-A with KoRV-B and/or -C), based on qPCR measurements of CD4, CD8b, IL-6, IL-10 and IL-17A mRNA expression in unstimulated and concanavalin (Con)-A-stimulated peripheral blood mononuclear cells (PBMCs). Although CD4, CD8b, and IL-17A expression did not differ between KoRV subtype infection profiles, IL-6 expression was higher in koalas with exogenous infections (both KoRV-B and KoRV-C) than those with the endogenous subtype only. IL-10 expression did not significantly differ between subtype infection profiles but did show a marked increase—accompanying decreased CD4:CD8b ratio—in a koala with lymphoma and co-infected with KoRV-A and -B, thus suggesting immunosuppression. Taken together, the findings of this study provide insights into koala immune response to multiple KoRV subtypes, which can be exploited for the development of prophylactic and therapeutic interventions for this iconic marsupial species.

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Greenwood, Alex D., and Alfred L. Roca. "Koala retrovirus (KoRV): molecular biology and evolution." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 11–14. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1607.

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Meers, Joanne, Greg Simmons, Kiersten Jones, Daniel T. W. Clarke, and Paul R. Young. "Koala retrovirus in free-ranging populations—prevalence." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 15–17. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1608.

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26

Fiebig, Uwe, Manuel Garcia Hartmann, Norbert Bannert, Reinhard Kurth, and Joachim Denner. "Transspecies Transmission of the Endogenous Koala Retrovirus." Journal of Virology 80, no. 11 (June 1, 2006): 5651–54. http://dx.doi.org/10.1128/jvi.02597-05.

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ABSTRACT The koala retrovirus (KoRV) is a gammaretrovirus closely related to the gibbon ape leukemia virus and induces leukemias and immune deficiencies associated with opportunistic infections, such as chlamydiosis. Here we characterize a KoRV newly isolated from an animal in a German zoo and show infection of human and rat cell lines in vitro and of rats in vivo, using immunological and PCR methods for virus detection. The KoRV transmembrane envelope protein (p15E) was cloned and expressed, and p15E-specific neutralizing antibodies able to prevent virus infection in vitro were developed. Finally, evidence for immunosuppressive properties of the KoRV was obtained.

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Fabijan, J., L. Woolford, S. Lathe, G. Simmons, F. Hemmatzadeh, D. J. Trott, and N. Speight. "Lymphoma, Koala Retrovirus Infection and Reproductive Chlamydiosis in a Koala ( Phascolarctos cinereus )." Journal of Comparative Pathology 157, no. 2-3 (August 2017): 188–92. http://dx.doi.org/10.1016/j.jcpa.2017.07.011.

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Hashem, Md Abul, Mohammad Enamul Hoque Kayesh, Fumie Maetani, Taiki Eiei, Kyoya Mochizuki, Shinsaku Ochiai, Ayaka Ito, et al. "Koala retrovirus (KoRV) subtypes and their impact on captive koala (Phascolarctos cinereus) health." Archives of Virology 166, no. 7 (April 26, 2021): 1893–901. http://dx.doi.org/10.1007/s00705-021-05078-y.

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Kayesh, Mohammad, Md Hashem, and Kyoko Tsukiyama-Kohara. "Toll-Like Receptor and Cytokine Responses to Infection with Endogenous and Exogenous Koala Retrovirus, and Vaccination as a Control Strategy." Current Issues in Molecular Biology 43, no. 1 (April 30, 2021): 52–64. http://dx.doi.org/10.3390/cimb43010005.

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Koala populations are currently declining and under threat from koala retrovirus (KoRV) infection both in the wild and in captivity. KoRV is assumed to cause immunosuppression and neoplastic diseases, favoring chlamydiosis in koalas. Currently, 10 KoRV subtypes have been identified, including an endogenous subtype (KoRV-A) and nine exogenous subtypes (KoRV-B to KoRV-J). The host’s immune response acts as a safeguard against pathogens. Therefore, a proper understanding of the immune response mechanisms against infection is of great importance for the host’s survival, as well as for the development of therapeutic and prophylactic interventions. A vaccine is an important protective as well as being a therapeutic tool against infectious disease, and several studies have shown promise for the development of an effective vaccine against KoRV. Moreover, CRISPR/Cas9-based genome editing has opened a new window for gene therapy, and it appears to be a potential therapeutic tool in many viral infections, which could also be investigated for the treatment of KoRV infection. Here, we discuss the recent advances made in the understanding of the immune response in KoRV infection, as well as the progress towards vaccine development against KoRV infection in koalas.

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Shojima, T., R. Yoshikawa, S. Hoshino, S. Shimode, S. Nakagawa, T. Ohata, R. Nakaoka, and T. Miyazawa. "Identification of a Novel Subgroup of Koala Retrovirus from Koalas in Japanese Zoos." Journal of Virology 87, no. 17 (July 3, 2013): 9943–48. http://dx.doi.org/10.1128/jvi.01385-13.

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Simmons, Greg, Joanne Meers, Daniel T. W. Clarke, Paul R. Young, Kiersten Jones, Jon J. Hanger, Jo Loader, and Jeff J. McKee. "The origins and ecological impact of koala retrovirus." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 31–33. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1610.

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Ishida, Yasuko, Chelsea McCallister, Nikolas Nikolaidis, Kyriakos Tsangaras, Kristofer M. Helgen, Alex D. Greenwood, and Alfred L. Roca. "Sequence variation of koala retrovirus transmembrane protein p15E among koalas from different geographic regions." Virology 475 (January 2015): 28–36. http://dx.doi.org/10.1016/j.virol.2014.10.036.

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Fabijan, J., N. Sarker, N. Speight, H. Owen, J. Meers, G. Simmons, J. Seddon, et al. "Pathological Findings in Koala Retrovirus-positive Koalas (Phascolarctos cinereus) from Northern and Southern Australia." Journal of Comparative Pathology 176 (April 2020): 50–66. http://dx.doi.org/10.1016/j.jcpa.2020.02.003.

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34

Xu, Wenquin, and Jonathan P. Stoye. "Koala retrovirus (KoRV): are humans at risk of infection?" Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 99–101. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1627.

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Sarker, Nishat, Jessica Fabijan, Jennifer Seddon, Rachael Tarlinton, Helen Owen, Greg Simmons, Joshua Thia, et al. "Genetic diversity of Koala retrovirus env gene subtypes: insights into northern and southern koala populations." Journal of General Virology 100, no. 9 (September 1, 2019): 1328–39. http://dx.doi.org/10.1099/jgv.0.001304.

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Fabijan, Jessica, Darren Miller, Olusola Olagoke, Lucy Woolford, Wayne Boardman, Peter Timms, Adam Polkinghorne, et al. "Prevalence and clinical significance of koala retrovirus in two South Australian koala (Phascolarctos cinereus) populations." Journal of Medical Microbiology 68, no. 7 (July 1, 2019): 1072–80. http://dx.doi.org/10.1099/jmm.0.001009.

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37

Alfano, Niccolò, Johan Michaux, Serge Morand, Ken Aplin, Kyriakos Tsangaras, Ulrike Löber, Pierre-Henri Fabre, et al. "Endogenous Gibbon Ape Leukemia Virus Identified in a Rodent (Melomys burtoni subsp.) from Wallacea (Indonesia)." Journal of Virology 90, no. 18 (July 6, 2016): 8169–80. http://dx.doi.org/10.1128/jvi.00723-16.

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ABSTRACTGibbon ape leukemia virus (GALV) and koala retrovirus (KoRV) most likely originated from a cross-species transmission of an ancestral retrovirus into koalas and gibbons via one or more intermediate as-yet-unknown hosts. A virus highly similar to GALV has been identified in an Australian native rodent (Melomys burtoni) after extensive screening of Australian wildlife. GALV-like viruses have also been discovered in several Southeast Asian species, although screening has not been extensive and viruses discovered to date are only distantly related to GALV. We therefore screened 26 Southeast Asian rodent species for KoRV- and GALV-like sequences, using hybridization capture and high-throughput sequencing, in the attempt to identify potential GALV and KoRV hosts. Only the individuals belonging to a newly discovered subspecies ofMelomysburtonifrom Indonesia were positive, yielding an endogenous provirus very closely related to a strain of GALV. The sequence of the critical receptor domain for GALV infection in the IndonesianM. burtonisubsp. was consistent with the susceptibility of the species to GALV infection. The second record of a GALV inM. burtoniprovides further evidence thatM. burtoni, and potentially other lineages within the widespread subfamilyMurinae, may play a role in the spread of GALV-like viruses. The discovery of a GALV in the most western part of the Australo-Papuan distribution ofM. burtoni, specifically in a transitional zone between Asia and Australia (Wallacea), may be relevant to the cross-species transmission to gibbons in Southeast Asia and broadens the known distribution of GALVs in wild rodents.IMPORTANCEGibbon ape leukemia virus (GALV) and the koala retrovirus (KoRV) are very closely related, yet their hosts neither are closely related nor overlap geographically. Direct cross-species infection between koalas and gibbons is unlikely. Therefore, GALV and KoRV may have arisen via a cross-species transfer from an intermediate host whose range overlaps those of both gibbons and koalas. Using hybridization capture and high-throughput sequencing, we have screened a wide range of rodent candidate hosts from Southeast Asia for KoRV- and GALV-like sequences. Only aMelomysburtonisubspecies from Wallacea (Indonesia) was positive for GALV. We report the genome sequence of this newly identified GALV, the critical domain for infection of its potential cellular receptor, and its phylogenetic relationships with the other previously characterized GALVs. We hypothesize thatMelomysburtoni, and potentially related lineages with an Australo-Papuan distribution, may have played a key role in cross-species transmission to other taxa.

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38

Witte, Carmel L. "Establishing priorities for research on the epidemiology of koala retrovirus (KoRV) in koalas (Phascolarctos cinereus)." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 61–63. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1618.

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Hobbs, Matthew, Ana Pavasovic, Andrew G. King, Peter J. Prentis, Mark DB Eldridge, Zhiliang Chen, Donald J. Colgan, et al. "A transcriptome resource for the koala (Phascolarctos cinereus): insights into koala retrovirus transcription and sequence diversity." BMC Genomics 15, no. 1 (2014): 786. http://dx.doi.org/10.1186/1471-2164-15-786.

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40

Fan, Hung. "Leukemogenesis by murine leukemia viruses: lessons for koala retrovirus (KoRV)." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 83–88. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1622.

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Simmons, GS, PR Young, JJ Hanger, K. Jones, D. Clarke, JJ McKee, and J. Meers. "Prevalence of koala retrovirus in geographically diverse populations in Australia." Australian Veterinary Journal 90, no. 10 (July 24, 2012): 404–9. http://dx.doi.org/10.1111/j.1751-0813.2012.00964.x.

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42

Kayesh, Mohammad Enamul Hoque, Md Abul Hashem, and Kyoko Tsukiyama-Kohara. "Koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (Phascolarctos cinereus): a review." Archives of Virology 165, no. 11 (August 8, 2020): 2409–17. http://dx.doi.org/10.1007/s00705-020-04770-9.

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43

Hayward, Joshua A., Mary Tachedjian, Claudia Kohl, Adam Johnson, Megan Dearnley, Brianna Jesaveluk, Christine Langer, et al. "Infectious KoRV-related retroviruses circulating in Australian bats." Proceedings of the National Academy of Sciences 117, no. 17 (April 13, 2020): 9529–36. http://dx.doi.org/10.1073/pnas.1915400117.

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Bats are reservoirs of emerging viruses that are highly pathogenic to other mammals, including humans. Despite the diversity and abundance of bat viruses, to date they have not been shown to harbor exogenous retroviruses. Here we report the discovery and characterization of a group of koala retrovirus-related (KoRV-related) gammaretroviruses in Australian and Asian bats. These include the Hervey pteropid gammaretrovirus (HPG), identified in the scat of the Australian black flying fox (Pteropus alecto), which is the first reproduction-competent retrovirus found in bats. HPG is a close relative of KoRV and the gibbon ape leukemia virus (GALV), with virion morphology and Mn2+-dependent virion-associated reverse transcriptase activity typical of a gammaretrovirus. In vitro, HPG is capable of infecting bat and human cells, but not mouse cells, and displays a similar pattern of cell tropism as KoRV-A and GALV. Population studies reveal the presence of HPG and KoRV-related sequences in several locations across northeast Australia, as well as serologic evidence for HPG in multiple pteropid bat species, while phylogenetic analysis places these bat viruses as the basal group within the KoRV-related retroviruses. Taken together, these results reveal bats to be important reservoirs of exogenous KoRV-related gammaretroviruses.

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44

Neil, James C. "How does koala retrovirus (KoRV) induce disease at the genomic level?" Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 57–58. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1616.

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Shojima, T., S. Hoshino, M. Abe, J. Yasuda, H. Shogen, T. Kobayashi, and T. Miyazawa. "Construction and Characterization of an Infectious Molecular Clone of Koala Retrovirus." Journal of Virology 87, no. 9 (February 20, 2013): 5081–88. http://dx.doi.org/10.1128/jvi.01584-12.

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46

Gillett, Amber K. "An examination of disease in captive Australian koalas (Phascolarctos cinereus) and potential links to koala retrovirus (KoRV)." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 39–45. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1612.

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McCallum, Hamish, Douglas H. Kerlin, William Ellis, and Frank Carrick. "Assessing the significance of endemic disease in conservation-koalas, chlamydia, and koala retrovirus as a case study." Conservation Letters 11, no. 4 (November 28, 2017): e12425. http://dx.doi.org/10.1111/conl.12425.

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Hashem, Md Abul, Mohammad Enamul Hoque Kayesh, Osamu Yamato, Fumie Maetani, Taiki Eiei, Kyoya Mochizuki, Hiroko Sakurai, et al. "Coinfection with koala retrovirus subtypes A and B and its impact on captive koalas in Japanese zoos." Archives of Virology 164, no. 11 (September 5, 2019): 2735–45. http://dx.doi.org/10.1007/s00705-019-04392-w.

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McMichael, L., C. Smith, A. Gordon, K. Agnihotri, J. Meers, and J. Oakey. "A novel Australian flying-fox retrovirus shares an evolutionary ancestor with Koala, Gibbon and Melomys gamma-retroviruses." Virus Genes 55, no. 3 (March 15, 2019): 421–24. http://dx.doi.org/10.1007/s11262-019-01653-3.

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Ivy, Jamie A. "Population management strategies for reducing koala retrovirus (KoRV) impacts on captive populations." Technical Reports of the Australian Museum, Online 24 (May 29, 2014): 97–98. http://dx.doi.org/10.3853/j.1835-4211.24.2014.1626.

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