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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 ...200010756041
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 ...200616501122
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 ...200616699047
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 ...200818818870
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 ...201120805639
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 ...201120829603
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 ...201425251014
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 ...201626905635
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 ...201424688858
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 ...201323249763
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 ...201728220345
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 ...201627999419
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 ...201627384662
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 ...201222694899
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.201526253512
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. ...201728704541
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 ...201526610552
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.201425214207
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 ...201829382557
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 ...201729237837
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 ...201829237726
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 ...201729158564
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 ...201728942303
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 ...201828669101
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 ...201728273935
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 ...201728266284
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 ...201727881645
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 ...201627706211
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.201627638778
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 ...201627468008
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 ...201627069793
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.201627054470
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 ...201526958909
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 ...201525925265
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 ...201525761531
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 ...201525596496
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 ...201525462343
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, ...201525261407
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 ...201424752422
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 ...201424239536
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.201323824806
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 ...201323651516
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 ...201323427161
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.201223004234
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 ...201322983950
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 ...200717870141
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.200617118218
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 ...200616823453
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 ...200515722540
infectious korv-related retroviruses circulating in australian bats.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 a ...202032284399
koala retrovirus diversity, transmissibility, and disease associations.koalas are infected with the koala retrovirus (korv) that exists as exogenous or endogenous viruses. korv is genetically diverse with co-infection with up to ten envelope subtypes (a-j) possible; korv-a is the prototype endogenous form. korv-b, first found in a small number of koalas with an increased leukemia prevalence at one us zoo, has been associated with other cancers and increased chlamydial disease. to better understand the molecular epidemiology of korv variants and the effect of increa ...202033008414
the relative contribution of causal factors in the transition from infection to clinical chlamydial disease.chlamydia is a major bacterial pathogen in humans and animals globally. yet 80% of infections never progress to clinical disease. decades of research have generated an interconnected network linking pathogen, host, and environmental factors to disease expression, but the relative importance of these and whether they account for disease progression remains unknown. to address this, we used structural equation modeling to evaluate putative factors likely to contribute to urogenital and ocular chla ...201829891934
koalas vaccinated against koala retrovirus respond by producing increased levels of interferon-gamma.koala retrovirus (korv) is believed to be in an active state of endogenization into the koala genome. korv is present as both an endogenous and exogenous infection in all koalas in northern australia. korv has been linked to koala pathologies including neoplasia and increased susceptibility to chlamydia. a korv vaccine recently trialled in 10 northern koalas improved antibody response and reduced viral load. this communication reports the expression of key immune genes underlining the innate and ...202033129323
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.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 an ...202032929174
koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (phascolarctos cinereus): a review.koala retrovirus (korv) is a major threat to koala health and conservation. it also represents a series of challenges across the fields of virology, immunology, and epidemiology that are of great potential interest to any researcher in the field of retroviral diseases. korv is a gammaretrovirus that is present in both endogenous and exogenous forms in koala populations, with a still-active endogenization process. korv may induce immunosuppression and neoplastic conditions such as lymphoma and le ...202032770481
therapeutic vaccination of koalas harbouring endogenous koala retrovirus (korv) improves antibody responses and reduces circulating viral load.the long-term survival of the koala is under serious threat from multiple factors, including infectious disease agents such as chlamydia and koala retrovirus (korv). korv is present in both exogenous and endogenous forms, depending on the geographical location of the population. in the northern half of australia, it is present as an endogenous infection in all koalas, making a case for an urgent need to develop a therapeutic vaccine that might prevent korv-associated pathologies in these koalas. ...202032699650
helping koalas battle disease - recent advances in chlamydia and koala retrovirus (korv) disease understanding and treatment in koalas.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, leadi ...202032556174
pathological findings in koala retrovirus-positive koalas (phascolarctos cinereus) from northern and southern australia.koala retrovirus (korv) infection shows differences in prevalence and load between northern and southern australian koala populations; however, the effect of this on diseases such as lymphoma and chlamydial disease is unclear. this study compared clinicopathological findings, haematology and splenic lymphoid area of korv-positive koalas from northern (queensland [qld], n = 67) and southern (south australia [sa], n = 92) populations in order to provide further insight into korv pathogenesis. bloo ...202032359636
transmission of koala retrovirus from parent koalas to a joey in a japanese zoo.koala retrovirus (korv) is of an interest to virologists due to its currently active endogenization into the koala (phascolarctos cinereus) genome. although korv has frequently been isolated in wild and captive koala populations, its pathogenesis and transmission remain to be fully characterized, and most previous research has concentrated on adult koalas rather than on joeys. here, we characterized korv isolates obtained from a deceased male joey and its parents (animals reared in a japanese zo ...202032188730
haematological reference intervals of wild southern australian koalas (phascolarctos cinereus).current haematology reference intervals (ris) for koalas were developed in northern australian koalas, using low numbers and/or individuals of unknown chlamydia pecorum and koala retrovirus (korv) status. this study developed haematological ris for wild, clinically healthy southern australian koalas of known c. pecorum and korv infection status and investigated the effects of population, age and sex.202032037511
novel insights into viral infection and oncogenesis from koala retrovirus (korv) infection of hek293t cells.koala retrovirus is thought to be an underlying cause of high levels of neoplasia and immunosuppression in koalas. while epidemiology studies suggest a strong link between korv and disease it has been difficult to prove causality because of the complex nature of the virus, which exists in both endogenous and exogenous forms. it has been difficult to identify koalas completely free of korv, and infection studies in koalas or koala cells are fraught with ethical and technical difficulties, respect ...202031972306
periodontal disease in free-ranging koalas (phascolarctos cinereus) from the mount lofty ranges, south australia, and its association with koala retrovirus infection.in northern australian koala populations (queensland and new south wales), periodontal disease (gingivitis and periodontitis) is common while koala retrovirus subtype a is endogenous, with other subtypes transmitted exogenously. koala retrovirus has been hypothesised to cause immune suppression and may predispose koalas to diseases caused by concurrent infections. in southern australia populations (victoria and south australia) periodontal disease has not been investigated, and koala retrovirus ...202031971256
koala retrovirus viral load and disease burden in distinct northern and southern koala populations.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 ...202031937823
coinfection with koala retrovirus subtypes a and b and its impact on captive koalas in japanese zoos.koala retrovirus (korv) is unique among endogenous retroviruses because its endogenization is still active. two major korv subtypes, korv-a and b, have been described, and korv-b is associated with disease and poses a health threat to koalas. here, we investigated the co-prevalence of korv-a and korv-b, detected by type-specific pcr and sequencing, and their impact on the health of koalas in three japanese zoos. we also investigated korv proviral loads and found varying amounts of genomic dna (g ...201931486907
antibody response against koala retrovirus (korv) in koalas harboring korv-a in the presence or absence of korv-b.koala retrovirus (korv) is in the process of endogenization into the koala (phascolarctos cinereus) genome and is currently spreading through the australian koala population. understanding how the koala's immune system responds to korv infection is critical for developing an efficacious vaccine to protect koalas. to this end, we analyzed the antibody response of 235 wild koalas, sampled longitudinally over a four-year period, that harbored korv-a, and with or without korv-b. we found that the ma ...201931455828
altered immune parameters associated with koala retrovirus (korv) and chlamydial infection in free ranging victorian koalas (phascolarctos cinereus).koala retrovirus (korv) has been widely speculated to cause immune suppression in koalas (phascolarctos cinereus) and to underlie the koala's susceptibility to infectious disease, however evidence for immunomodulation is limited. the aim of this study is to determine whether immunophenotypic changes are associated with korv infection in free ranging victorian koalas. qpcr was used to examine mrna expression for th1 (ifnγ), th2-promoting (il6, il10) and th17 (il17a) cytokines, along with cd4 and ...201931371797
genetic diversity of koala retrovirus env gene subtypes: insights into northern and southern koala populations.koala retrovirus (korv) is a recently endogenized retrovirus associated with neoplasia and immunosuppression in koala populations. the virus is known to display sequence variability and to be present at varying prevalence in different populations, with animals in southern australia displaying lower prevalence and viral loads than northern animals. this study used a pcr and next-generation sequencing strategy to examine the diversity of the korv env gene in both proviral dna and viral rna forms i ...201931329088
clinical and pathological characteristics of acute myelogenous leukemia in a female koala with diabetes mellitus.a female koala presented with hyperglycemia related to diabetes mellitus diagnosed at 9 years and treated with insulin. she presented with nasal hemorrhage, anemia, leukocytosis, and tachypnea at 10 years. a blood smear examination revealed scattered, atypical large myeloid cells and a clinical diagnosis of myelogenous leukemia was made. white blood cell count reached a maximum of 295 × 102/µl, with evidence of severe regenerative anemia and thrombocytopenia. grossly, systemic lymph node enlarge ...201931270282
changes in endogenous and exogenous koala retrovirus subtype expression over time reflect koala health outcomes.koala retrovirus (korv) is unique in that it exists as both an exogenous and actively endogenizing gamma retrovirus of koalas. while nine subtypes of korv have been recognized, focused study of these subtypes in koalas over time and with different health outcomes has been lacking. therefore, in this study, three wild koala cohorts were established and monitored to examine korv proviral and expression data from koalas that either remained healthy over time, began healthy before developing chlamyd ...201931243137
prevalence and clinical significance of koala retrovirus in two south australian koala (phascolarctos cinereus) populations.koala retrovirus (korv-a) is 100  % prevalent in northern australian (queensland and new south wales) koala populations, where korv-b has been associated with chlamydia pecorum disease and the development of lymphosarcoma. in southern populations (victoria and south australia), korv-a is less prevalent and korv-b has not been detected in victoria, while the current prevalence in south australian populations is unknown but is thought to be low. this study aimed to determine (i) the prevalence of ...201931162024
molecular dynamics of koala retrovirus infection in captive koalas in japan.koala retrovirus (korv) is a gammaretrovirus that is becoming endogenous in koalas. here, we explored the dynamics of korv infection in captive koalas in japan. we isolated peripheral blood mononuclear cells (pbmcs) from 11 koalas, from which we extracted the korv genome. we found the prevalence of korv provirus in the koalas to be 100%, and the copy number of korv proviral dna in genomic dna isolated from pbmcs was variable. the korv envelope genes from 11 koalas were sequenced and all were fou ...201930656465
detection and differentiation of two koala gammaherpesviruses by use of high-resolution melt (hrm) analysis reveals differences in viral prevalence and clinical associations in a large study of free-ranging koalas.the iconic koala (phascolarctos cinereus) is host to two divergent gammaherpesviruses, phascolarctid gammaherpesviruses 1 and 2 (phahv-1 and -2), but the clinical significance of the individual viruses is unknown and current diagnostic methods are unsuitable for differentiating between the viruses in large-scale studies. to address this, we modified a pan-herpesvirus nested pcr to incorporate high-resolution melt analysis. we applied this assay in a molecular epidemiological study of 810 koalas ...201930626662
therapeutic effect of a chlamydia pecorum recombinant major outer membrane protein vaccine on ocular disease in koalas (phascolarctos cinereus).chlamydia pecorum is responsible for causing ocular infection and disease which can lead to blindness in koalas (phascolarctos cinereus). antibiotics are the current treatment for chlamydial infection and disease in koalas, however, they can be detrimental for the koala's gastrointestinal tract microbiota and in severe cases, can lead to dysbiosis and death. in this study, we evaluated the therapeutic effects provided by a recombinant chlamydial major outer membrane protein (momp) vaccine on ocu ...201930615687
induction of neutralizing antibody response against koala retrovirus (korv) and reduction in viral load in koalas following vaccination with recombinant korv envelope protein.koala retrovirus (korv) infects the majority of australia's koalas (phascolarctos cinereus) and has been linked to several life-threatening diseases such as lymphoma and leukemia, as well as chlamydia and thus poses a threat to the continued survival of this species. while quarantine and antiretroviral drug treatment are possible control measures, they are impractical, leaving vaccination as the only realistic option. in this study, we examined the effect of a recombinant envelope protein-based ...201830083396
degradation and remobilization of endogenous retroviruses by recombination during the earliest stages of a germ-line invasion.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), permittin ...201830082403
molecular diagnosis of koala retrovirus (korv) in south australian koalas (phascolarctos cinereus).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 stat ...202134065572
toll-like receptor and cytokine responses to infection with endogenous and exogenous koala retrovirus, and vaccination as a control strategy.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 mech ...202133946297
toll-like receptor expression profiles in koala (phascolarctos cinereus) peripheral blood mononuclear cells infected with multiple korv subtypes.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 subt ...202133915914
koala retrovirus (korv) subtypes and their impact on captive koala (phascolarctos cinereus) health.koala retrovirus (korv), a major pathogen of koalas, exists in both endogenous (korv-a) and exogenous forms (korv-b to j). however, the impact of infection with multiple subtypes is not well understood. accordingly, in this study, we surveyed a representative sample from a japanese zoo population to determine the infection status for three korv subtypes (korv-a, b, and c) and to investigate the proviral and rna load profiles in animals with single- and multiple-subtype infections, using peripher ...202133900468
retroviral integrations contribute to elevated host cancer rates during germline invasion.repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. however, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. here we examine retroviral endogenisation during its earliest stages in the koala (phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (korv) and affected by high cancer prevalence. we characterise korv integ ...202133637755
a natural laboratory to elucidate the evolution of endogenous-exogenous retroviral interactions.the advent of whole genome sequencing has revealed much about the genomes of animals including the relatively large percentage of the genome consisting of endogenous retroviruses (erv; international human genome sequencing consortium, 2001). an erv arises when a retrovirus integrates into a host germ cell genome through normal infection processes. germline infections can be transmitted to offspring through mendelian inheritance and at times become fixed elements of the host genome (weiss, 2006). ...202133599349
koala retrovirus in northern australia shows a mixture of stable endogenization and exogenous lineage diversification within fragmented koala populations.the koala population in northern australia has become increasingly fragmented due to natural and man-made barriers and interventions. this situation has created a unique opportunity to study both endogenous and exogenous koala retrovirus (korv). to determine the impact that population isolation has had on korv diversity in queensland, 272 koalas from six fragmented koala populations were profiled for their korv provirus across two natural biogeographical barriers (the st lawrence gap and the bri ...202133472936
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.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) ...202033316950
endogenous retroviruses drive resistance and promotion of exogenous retroviral homologs.endogenous retroviruses (ervs) serve as markers of ancient viral infections and provide invaluable insight into host and viral evolution. ervs have been exapted to assist in performing basic biological functions, including placentation, immune modulation, and oncogenesis. a subset of ervs share high nucleotide similarity to circulating horizontally transmitted exogenous retrovirus (xrv) progenitors. in these cases, erv-xrv interactions have been documented and include (a) recombination to result ...202033290087
phylogenetic and geographical analysis of a retrovirus during the early stages of endogenous adaptation and exogenous spread in a new host.most retroviral endogenization and host adaptation happened in the distant past, with the opportunity to study these processes as they occurred lost to time. an exception exists with the discovery that koala retrovirus (korv) has recently begun its endogenization into the koala (phascolarctos cinereus) genome. what makes this opportunity remarkable is the fact that northern australian koalas appear to be undergoing endogenization with one korv subtype (korv-a), while all subtypes (korv-a-i) coex ...202033219558
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