Publications

the nucleotide sequence of koala (phascolarctos cinereus) retrovirus: a novel type c endogenous virus related to gibbon ape leukemia virus.	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 sequen ...	2000	10756041
real-time reverse transcriptase pcr for the endogenous koala retrovirus reveals an association between plasma viral load and neoplastic disease in koalas.	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 ...	2005	15722540
koala retrovirus: a genome invasion in real time.	koalas are currently undergoing a wave of germline infections by the retrovirus korv. study of this phenomenon not only provides an opportunity for understanding the processes regulating retrovirus endogenization but may also be essential to preventing the extinction of the species.	2006	17118218
retroviral invasion of the koala genome.	endogenous retroviruses are a common ancestral feature of mammalian genomes with most having been inactivated over time through mutation and deletion. a group of more intact endogenous retroviruses are considered to have entered the genomes of some species more recently, through infection by exogenous viruses, but this event has never been directly proved. we have previously reported koala retrovirus (korv) to be a functional virus that is associated with neoplasia. here we show that korv also s ...	2006	16823453
in vitro characterization of a koala retrovirus.	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 i ...	2006	16501122
transspecies transmission of the endogenous koala retrovirus.	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-sp ...	2006	16699047
transspecies transmissions of retroviruses: new cases.	transspecies transmission is common among retroviruses, although the consequences of the transmission are very different. some transspecies transmissions have resulted in fatal diseases in the new host while others have remained asymptomatic. some retroviruses are apathogenic in the original species, but pathogenic in a new host and others can be pathogenic or apathogenic in both species. in some cases, endogenization of the retrovirus in the new host has been observed but in others not, while s ...	2007	17870141
biology and evolution of the endogenous koala retrovirus.	although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. koala retrovirus (korv) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to n ...	2008	18818870
isolation of koala retroviruses from koalas in japan.	koala retrovirus (korv) is considered to be associated with leukemia, lymphoma and immunodeficiency-like diseases in koalas. we therefore conducted a pilot study of korv infection in five queensland koalas in kobe municipal oji zoo. by polymerase chain reaction to detect partial env and pol genes of korv in genomic dna isolated from whole blood and feces, all five koalas were found to be positive for korv proviruses. we succeeded in culturing koala lymphocytes from less than 1 ml blood for over ...	2011	20805639
increased neutralizing antibody response after simultaneous immunization with leucogen and the feline leukemia virus transmembrane protein.	to develop improved vaccination strategies against feline leukemia virus (felv), rats were immunized with the transmembrane envelope protein p15e of felv alone or in combination with the commercial vaccine leucogen® comprising the nonglycosylated felv surface envelope protein. binding and neutralizing antibodies were induced in both groups and in the group immunized with leucogen alone. higher titers of antibodies neutralizing felv were induced by simultaneous immunization with leucogen and p15e ...	2011	20829603
identification of diverse groups of endogenous gammaretroviruses in mega- and microbats.	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 gammaret ...	2012	22694899
prevalence of koala retrovirus in geographically diverse populations in australia.	to determine the prevalence of koala retrovirus (korv) in selected koala populations and to estimate proviral copy number in a subset of koalas.	2012	23004234
one hundred twenty years of koala retrovirus evolution determined from museum skins.	although endogenous retroviruses are common across vertebrate genomes, the koala retrovirus (korv) is the only retrovirus known to be currently invading the germ line of its host. korv is believed to have first infected koalas in northern australia less than two centuries ago. we examined korv in 28 koala museum skins collected in the late 19th and 20th centuries and deep sequenced the complete proviral envelope region from five northern australian specimens. strikingly, korv env sequences were ...	2013	22983950
identification of a novel subgroup of koala retrovirus from koalas in japanese zoos.	we identified a new subgroup of koala retrovirus (korv), named korv-j, which utilizes thiamine transport protein 1 as a receptor instead of the pit-1 receptor used by korv (korv-a). by subgroup-specific pcr, korv-j and korv-a were detected in 67.5 and 100% of koalas originating from koalas from northern australia, respectively. altogether, our results indicate that the invasion of the koala population by korv-j may have occurred more recently than invasion by korv-a.	2013	23824806
identification of cellular factors required for the budding of koala retrovirus.	koala retrovirus (korv) is a unique gammaretrovirus that is currently endogenizing into its host and considered to be associated with leukemia, lymphoma and immunosuppression in koalas (phascolactos cinereus). in this study, it was demonstrated that wwp2 or wwp2-like e3 ubiquitin ligases possessing the ww domain closely related to wwp2 and vps4a/b are involved in korv budding. these data suggest that korv gag recruits the cellular endosomal sorting complex required for transport machinery throug ...	2013	23651516
construction and characterization of an infectious molecular clone of koala retrovirus.	koala retrovirus (korv) is a gammaretrovirus that is currently endogenizing into koalas. studies on korv infection have been hampered by the lack of a replication-competent molecular clone. in this study, we constructed an infectious molecular clone, termed plasmid pkorv522, of a korv isolate (strain aki) from a koala reared in a japanese zoo. the virus korv522, derived from pkorv522, grew efficiently in human embryonic kidney (hek293t) cells, attaining 10(6) focus-forming units/ml. several muta ...	2013	23427161
immunising with the transmembrane envelope proteins of different retroviruses including hiv-1: a comparative study.	the induction of neutralizing antibodies is a promising way to prevent retrovirus infections. neutralizing antibodies are mainly directed against the envelope proteins, which consist of two molecules, the surface envelope (su) protein and the transmembrane envelope (tm) protein. antibodies broadly neutralizing the human immunodeficiencvy virus-1 (hiv-1) and binding to the tm protein gp41 of the virus have been isolated from infected individuals. their epitopes are located in the membrane proxima ...	2013	23249763
expression profiles of the immune genes cd4, cd8β, ifnγ, il-4, il-6 and il-10 in mitogen-stimulated koala lymphocytes (phascolarctos cinereus) by qrt-pcr.	investigation of the immune response of the koala (phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is chlamydial disease, caused by chlamydia pecorum and chlamydia pneumoniae. in addition, koala retrovirus (korv), which is of 100% prevalence in northern australia, has been ...	2014	24688858
discovery of a novel retrovirus sequence in an australian native rodent (melomys burtoni): a putative link between gibbon ape leukemia virus and koala retrovirus.	gibbon ape leukaemia virus (galv) and koala retrovirus (korv) share a remarkably close sequence identity despite the fact that they occur in distantly related mammals on different continents. it has previously been suggested that infection of their respective hosts may have occurred as a result of a species jump from another, as yet unidentified vertebrate host. to investigate possible sources of these retroviruses in the australian context, dna samples were obtained from 42 vertebrate species a ...	2014	25251014
a transcriptome resource for the koala (phascolarctos cinereus): insights into koala retrovirus transcription and sequence diversity.	the koala, phascolarctos cinereus, is a biologically unique and evolutionarily distinct australian arboreal marsupial. the goal of this study was to sequence the transcriptome from several tissues of two geographically separate koalas, and to create the first comprehensive catalog of annotated transcripts for this species, enabling detailed analysis of the unique attributes of this threatened native marsupial, including infection by the koala retrovirus.	2014	25214207
hybridization capture reveals evolution and conservation across the entire koala retrovirus genome.	the koala retrovirus (korv) is the only retrovirus known to be in the midst of invading the germ line of its host species. hybridization capture and next generation sequencing were used on modern and museum dna samples of koala (phascolarctos cinereus) to examine ca. 130 years of evolution across the full korv genome. overall, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. a total of 138 polymorphisms were detecte ...	2014	24752422
heterogeneity of koala retrovirus isolates.	koala retrovirus (korv) is a gammaretrovirus which may induce immune suppression, leukemia and lymphoma in koalas. currently three korv subgroups (a, b, and j) have been reported. our phylogenetic analysis suggests that korv-b and korv-j should be classified as the same subgroup. in long terminal repeat (ltr), a korv-b isolate has four 17 bp tandem repeats named direct repeat (dr)-1, while a korv-j isolate (strain oj-4) has three 37 bp tandem repeats named dr-2. we also found that the promoter a ...	2014	24239536
koala retroviruses: evolution and disease dynamics.	a retroviral etiology for malignant neoplasias in koalas has long been suspected. evidence for retroviral involvement was bolstered in 2000 by the isolation of a koala retrovirus (korv), now termed korv-a. korv-a is an endogenous retrovirus-a retrovirus that infects germ cells-a feature that makes it a permanent resident of the koala genome. korv-a lacks the genetic diversity of an exogenous retrovirus, a quality associated with the ability of a retrovirus to cause neoplasias. in 2013, a second ...	2015	26958909
induction of neutralizing antibodies specific for the envelope proteins of the koala retrovirus by immunization with recombinant proteins or with dna.	the koala retrovirus (korv) is the result of a transspecies transmission of a gammaretrovirus with fatal consequences for the new host. like many retroviruses, korv induces lymphoma, leukemia and an immunodeficiency that is associated with opportunistic infections in the virus-infected animals. we recently reported the induction of neutralizing antibodies by immunization with the recombinant ectodomain of the transmembrane envelope protein p15e of korv. since the neutralization titers of the p15 ...	2015	25925265
immunomics of the koala (phascolarctos cinereus).	the study of the koala transcriptome has the potential to advance our understanding of its immunome--immunological reaction of a given host to foreign antigens--and to help combat infectious diseases (e.g., chlamydiosis) that impede ongoing conservation efforts. we used illumina sequencing of cdna to characterize genes expressed in two different koala tissues of immunological importance, blood and spleen. we generated nearly 600 million raw sequence reads, and about 285 million of these were sub ...	2015	25761531
lack of antiviral antibody response in koalas infected with koala retroviruses (korv).	many wild koalas are infected with the koala retrovirus, korv, some of which suffer from lymphoma and chlamydial disease. three subgroups, korv-a, korv-b and korv-j, have so far been described. it is well known that other closely related gammaretroviruses can induce tumours and severe immunodeficiencies in their respective hosts and a possible role for korv infection in lymphoma and chlamydial disease in koalas has been suggested. in many wild koalas, korv-a has become endogenised, i.e., it is i ...	2015	25596496
sequence variation of koala retrovirus transmembrane protein p15e among koalas from different geographic regions.	the koala retrovirus (korv), which is transitioning from an exogenous to an endogenous form, has been associated with high mortality in koalas. for other retroviruses, the envelope protein p15e has been considered a candidate for vaccine development. we therefore examined proviral sequence variation of korv p15e in a captive queensland and three wild southern australian koalas. we generated 163 sequences with intact open reading frames, which grouped into 39 distinct haplotypes. sixteen distinct ...	2015	25462343
proliferation of endogenous retroviruses in the early stages of a host germ line invasion.	endogenous retroviruses (ervs) comprise 8% of the human genome and are common in all vertebrate genomes. the only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (korv), making koalas (phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. to distinguish endogenous from exogenous korv proviruses, we isolated koala genomic regions flanking korv integration sites. in three wild southern australian koalas, ...	2015	25261407
an evolutionarily young polar bear (ursus maritimus) endogenous retrovirus identified from next generation sequence data.	transcriptome analysis of polar bear (ursus maritimus) tissues identified sequences with similarity to porcine endogenous retroviruses (perv). based on these sequences, four proviral copies and 15 solo long terminal repeats (ltrs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. closely related sequences were identified by pcr analysis of brown bear (ursus arctos) and black bear (ursus americanus) but were absent in non-ursinae bear species ...	2015	26610552
human and murine apobec3s restrict replication of koala retrovirus by different mechanisms.	koala retrovirus (korv) is an endogenous and exogenous retrovirus of koalas that may cause lymphoma. as for many other gammaretroviruses, the korv genome can potentially encode an alternate form of gag protein, glyco-gag.	2015	26253512
transspecies transmission of gammaretroviruses and the origin of the gibbon ape leukaemia virus (galv) and the koala retrovirus (korv).	transspecies transmission of retroviruses is a frequent event, and the human immunodeficiency virus-1 (hiv-1) is a well-known example. the gibbon ape leukaemia virus (galv) and koala retrovirus (korv), two gammaretroviruses, are also the result of a transspecies transmission, however from a still unknown host. related retroviruses have been found in southeast asian mice although the sequence similarity was limited. viruses with a higher sequence homology were isolated from melomys burtoni, the a ...	2016	27999419
endogenous gibbon ape leukemia virus identified in a rodent (melomys burtoni subsp.) from wallacea (indonesia).	gibbon 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 viru ...	2016	27384662
characterisation of cd4 t cells in healthy and diseased koalas (phascolarctos cinereus) using cell-type-specific monoclonal antibodies.	the koala (phascolarctos cinereus) is an arboreal herbivorous marsupial that is an australian icon. koalas in many parts of australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as chlamydia spp. and the koala retrovirus (korv), which may contribute to the incidence of lymphoma and leukaemia in this species. due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the im ...	2016	26905635
altered immune cytokine expression associated with korv b infection and season in captive koalas.	koala (phascolarctos cinereus) populations are increasingly vulnerable and one of the main threats is chlamydial infection. koala retrovirus (korv) has been proposed as an underlying cause of the koala's susceptibility to infection with chlamydia and high rates of lymphoid neoplasia; however, the regionally ubiquitous, endogenous nature of this virus suggests that korv a infection is not sufficient for immune suppression to occur. a recently discovered exogenous variant of korv, korv b, has seve ...	2016	27706211
detection of koala retrovirus subgroup b (korv-b) in animals housed at european zoos.	many koalas carry an endogenous retrovirus, korv-a, in their genome. recently, a second retrovirus, korv-b, was detected in koalas in japanese and u.s. zoos. however, this virus is not endogenous, differs in the receptor binding site of the surface envelope protein, and uses a receptor different from that of korv-a. we describe here a korv-b found in koalas at zoos in germany and belgium that differs slightly from that found in the los angeles zoo.	2016	27638778
koala retrovirus: a review.	koala retrovirus (korv) is a gammaretrovirus that has been identified in both captive and free-ranging koalas ( phascolarctos cinereus ) with variable geographic distribution in australia. korv is capable of both exogenous and endogenous transmission, which provides an interesting research platform for scientists to study active retrovirus endogenization into a host genome and offers veterinary scientists an opportunity to examine the clinical consequences of korv infection in koalas. causation ...	2016	27468008
comprehensive profiling of retroviral integration sites using target enrichment methods from historical koala samples without an assembled reference genome.	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 tra ...	2016	27069793
serum antibody response to koala retrovirus antigens varies in free-ranging koalas ( phascolarctos cinereus ) in australia: implications for vaccine design.	little is known about the immune response in the koala ( phascolarctos cinereus ) to its retroviruses. koala retroviruses (korvs) have been linked to neoplasia in wild and captive koalas, but there is no treatment available. we tested the korv-specific serum immunoglobulin g antibody response in nonimmunized and immunized koalas.	2016	27054470
koala retrovirus (korv) genotyping analyses reveal a low prevalence of korv-a in victorian koalas and an association with clinical disease.	koala retrovirus (korv) is currently undergoing endogenisation into the genome of koalas in australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. the prevalence of korv in north eastern australia (queensland and new south wales) is 100%, whereas previous preliminary investigations in south eastern australia (victoria) suggested korv is present at a lower prevalence, although the values have varied widely. here we describe a large study of ...	2016	28032537
phylogenetic diversity of koala retrovirus within a wild koala population.	koala populations are in serious decline across many areas of mainland australia, with infectious disease a contributing factor. koala retrovirus (korv) is a gammaretrovirus present in most wild koala populations and captive colonies. five subtypes of korv (a to e) have been identified based on amino acid sequence divergence in a hypervariable region of the receptor binding domain of the envelope protein. however, analysis of viral genetic diversity has been conducted primarily on korv in captiv ...	2017	27881645
molecular dynamics and mode of transmission of koala retrovirus (korv) as it invades and spreads through a wild queensland koala population.	the recent acquisition of a novel retrovirus (korv) by koalas (phascolarctos cinereus) has created new opportunities for retroviral research and new challenges for koala conservation. there are currently two major subtypes of korv; korv-a, which is believed to be endogenous only in koalas from the northern part of australia, and korv-b, which appears to be exogenous. understanding and management of these subtypes requires population-level studies of their prevalence and diversity, especially whe ...	2017	29237837
long-read genome sequence assembly provides insight into ongoing retroviral invasion of the koala germline.	the koala retrovirus (korv) is implicated in several diseases affecting the koala (phascolarctos cinereus). korv provirus can be present in the genome of koalas as an endogenous retrovirus (present in all cells via germline integration) or as exogenous retrovirus responsible for somatic integrations of proviral korv (present in a limited number of cells). this ongoing invasion of the koala germline by korv provides a powerful opportunity to assess the viral strategies used by korv in an individu ...	2017	29158564
lymphoma, koala retrovirus infection and reproductive chlamydiosis in a koala (phascolarctos cinereus).	koala retrovirus (korv) infection, thought to be associated with lymphoid neoplasia, and chlamydia pecorum-related ocular and urogenital disease are both highly prevalent in eastern australian koala (phascolarctos cinereus) populations. however, in south australian koalas, little is known about korv infection and c. pecorum-associated disease. we report the first south australian case of lymphoma in a korv-a-positive female koala also affected by severe reproductive chlamydiosis. the koala was f ...	2017	28942303
infection with koala retrovirus subgroup b (korv-b), but not korv-a, is associated with chlamydial disease in free-ranging koalas (phascolarctos cinereus).	the virulence of chlamydial infection in wild koalas is highly variable between individuals. some koalas can be infected (pcr positive) with chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (korv). retroviruses can be immunosuppressive, and there is evidence of an immunosuppress ...	2017	28273935
koala retrovirus genotyping analyses reveal a low prevalence of korv-a in victorian koalas and an association with clinical disease.	koala retrovirus (korv) is undergoing endogenization into the genome of koalas in australia, providing an opportunity to assess the effect of retrovirus infection on the health of a population. the prevalence of korv in north-eastern australia (queensland and new south wales) is 100 %, whereas previous preliminary investigations in south-eastern australia (victoria) suggested korv is present at a lower prevalence, although the values have varied widely. here, we describe a large study of free-ra ...	2017	28266284
a new look at the origins of gibbon ape leukemia virus.	is the origin of gibbon ape leukemia virus (galv) human after all? when galv was discovered and found to cause neoplastic disease in gibbons, it stimulated a great deal of research including investigations into the origins of this virus. a number of publications have suggested that the galv progenitor was a retrovirus present in one of several species of south east asian rodents that had close contact with captive gibbons. however, there are no published retroviral sequences from any south east ...	2017	28220345
increased genetic diversity and prevalence of co-infection with trypanosoma spp. in koalas (phascolarctos cinereus) and their ticks identified using next-generation sequencing (ngs).	infections with trypanosoma spp. have been associated with poor health and decreased survival of koalas (phascolarctos cinereus), particularly in the presence of concurrent pathogens such as chlamydia and koala retrovirus. the present study describes the application of a next-generation sequencing (ngs)-based assay to characterise the prevalence and genetic diversity of trypanosome communities in koalas and two native species of ticks (ixodes holocyclus and i. tasmani) removed from koala hosts. ...	2017	28704541
characterisation of mhc class i genes in the koala.	koala (phascolarctos cinereus) populations are on the decline across the majority of australia's mainland. two major diseases threatening the long-term survival of affected koala populations are caused by obligate intracellular pathogens: chlamydia and koala retrovirus (korv). to improve our understanding of the koala immune system, we characterised their major histocompatibility complex (mhc) class i genes, which are centrally involved in presenting foreign peptides derived from intracellular p ...	2018	28669101
transmission, evolution, and endogenization: lessons learned from recent retroviral invasions.	viruses of the subfamilyorthoretrovirinaeare defined by the ability to reverse transcribe an rna genome into dna that integrates into the host cell genome during the intracellular virus life cycle. exogenous retroviruses (xrvs) are horizontally transmitted between host individuals, with disease outcome depending on interactions between the retrovirus and the host organism. when retroviruses infect germ line cells of the host, they may become endogenous retroviruses (ervs), which are permanent el ...	2018	29237726
koala immunology and infectious diseases: how much can the koala bear?	infectious diseases are contributing to the decline of the iconic australian marsupial, the koala (phascolarctos cinereus). infections with the obligate intracellular bacteria, chlamydia pecorum, cause debilitating ocular and urogenital-tract disease while the koala-retrovirus (korv) has been implicated in host immunosuppression and exacerbation of chlamydial pathogenesis. although histological studies have provided insight into the basic architecture of koala immune tissues, our understanding o ...	2018	29382557