An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo

Xu, W.; Stadler, Cynthia K.; Gorman, Kristen F.; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M.; Pye, Geoffrey W.; Eiden, Maribeth V.

doi:10.1073/pnas.1304704110

Cited by 129 publications

(305 citation statements)

References 21 publications

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“…High levels of expression are seen in newborn joeys, but it remains unclear whether this results from the endogenous virus or the concomitant exogenous virus spreading. KoRV expression is associated with lymphomas in captive koalas (64). However, here the relative contributions of endogenous and exogenous virus are also unclear.…”

Section: Acquisition and Amplificationmentioning

confidence: 99%

Mammalian Endogenous Retroviruses

Mager

Stoye²

2015

Microbiol Spectr

165

103

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Over 40% of mammalian genomes comprise the products of reverse transcription. Among such retrotransposed sequences are those characterized by the presence of long terminal repeats (LTRs), including the endogenous retroviruses (ERVs), which are inherited genetic elements closely resembling the proviruses formed following exogenous retrovirus infection. Sequences derived from ERVs make up at least 8 to 10% of the human and mouse genomes and range from ancient sequences that predate mammalian divergence to elements that are currently still active. In this chapter we describe the discovery, classification and origins of ERVs in mammals and consider cellular mechanisms that have evolved to control their expression. We also discuss the negative effects of ERVs as agents of genetic disease and cancer and review examples of ERV protein domestication to serve host functions, as in placental development. Finally, we address growing evidence that the gene regulatory potential of ERV LTRs has been exploited multiple times during evolution to regulate genes and gene networks. Thus, although recently endogenized retroviral elements are often pathogenic, those that survive the forces of negative selection become neutral components of the host genome or can be harnessed to serve beneficial roles.

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Section: Acquisition and Amplificationmentioning

confidence: 99%

Mammalian Endogenous Retroviruses

Mager

Stoye²

2015

Microbiol Spectr

165

103

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“…Consequently, it may be worthwhile to screen indigenous Australian bats and rodents for gammaretroviruses and associated ERVs to elucidate further on the possible intermediate vector of KoRV. It is also worth noting that KoRV recently was shown to exist in two subtypes (KoRV-A and -B), with different genomic structures, cell receptor use, and suggested pathology (16), which further complicates tracing of the distribution and potential transmission routes of KoRV.…”

Section: Significancementioning

confidence: 99%

“…We use the resultant ERVs to address several issues of current importance in gammaretrovirus biology and draw unique insights in gammaretrovirus-host evolution. As an example, we focus on koala retrovirus (KoRV), which is widespread among wild and captive koala populations and is linked with disease symptoms (16,17). The source of the infection of koalas with KoRV is unknown, but KoRV is hypothesized to have arisen as a consequence of a recent cross-species transmission event during the last 200 y, possibly from Asian mice (7,18).…”

Section: Significancementioning

confidence: 99%

Broad-scale phylogenomics provides insights into retrovirus–host evolution

Hayward

Grabherr

Jern

2013

Proc. Natl. Acad. Sci. U.S.A.

130

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Genomic data provide an excellent resource to improve understanding of retrovirus evolution and the complex relationships among viruses and their hosts. In conjunction with broad-scale in silico screening of vertebrate genomes, this resource offers an opportunity to complement data on the evolution and frequency of past retroviral spread and so evaluate future risks and limitations for horizontal transmission between different host species. Here, we develop a methodology for extracting phylogenetic signal from large endogenous retrovirus (ERV) datasets by collapsing information to facilitate broad-scale phylogenomics across a wide sample of hosts. Starting with nearly 90,000 ERVs from 60 vertebrate host genomes, we construct phylogenetic hypotheses and draw inferences regarding the designation, host distribution, origin, and transmission of the Gammaretrovirus genus and associated class I ERVs. Our results uncover remarkable depths in retroviral sequence diversity, supported within a phylogenetic context. This finding suggests that current infectious exogenous retrovirus diversity may be underestimated, adding credence to the possibility that many additional exogenous retroviruses may remain to be discovered in vertebrate taxa. We demonstrate a history of frequent horizontal interorder transmissions from a rodent reservoir and suggest that rats may have acted as important overlooked facilitators of gammaretrovirus spread across diverse mammalian hosts. Together, these results demonstrate the promise of the methodology used here to analyze large ERV datasets and improve understanding of retroviral evolution and diversity for utilization in wider applications.

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“…293T human embryonic kidney cells (ATCC CCL 11268) and murine Mus dunni tail fibroblast MDTF cells (35) were maintained in Dulbecco modified Eagle medium with high glucose, supplied with 10% fetal bovine serum, 100 U of penicillin/ml, and 100 g of streptomycin/ml. MDTF cells expressing human PiT1 and human THTR1 individually were described previously (36).…”

Section: Pcrmentioning

confidence: 99%

Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape Leukemia Virus and Related Gammaretroviruses

Alfano

Kolokotronis

Tsangaras

et al. 2016

J Virol

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Gibbon ape leukemia viruses (GALVs) are part of a larger group of pathogenic gammaretroviruses present across phylogenetically diverse host species of Australasian mammals. Despite the biomedical utility of GALVs as viral vectors and in cancer gene therapy, full genome sequences have not been determined for all of the five identified GALV strains, nor has a comprehensive evolutionary analysis been performed. We therefore generated complete genomic sequences for each GALV strain using hybridization capture and high-throughput sequencing. The four strains of GALV isolated from gibbons formed a monophyletic clade that was closely related to the woolly monkey virus (WMV), which is a GALV strain that likely originated in a gibbon host. The GALV-WMV clade in turn formed a sister group to the koala retroviruses (KoRVs). Genomic signatures of episodic diversifying selection were detected among the gammaretroviruses with concentration in the env gene across the GALV strains that were particularly oncogenic and KoRV strains that were potentially exogenous, likely reflecting their adaptation to the host immune system. In vitro studies involving vectors chimeric between GALV and KoRV-B established that variable regions A and B of the surface unit of the envelope determine which receptor is used by a viral strain to enter host cells. IMPORTANCEThe gibbon ape leukemia viruses (GALVs) are among the most medically relevant retroviruses due to their use as viral vectors for gene transfer and in cancer gene therapy. Despite their importance, full genome sequences have not been determined for the majority of primate isolates, nor has comprehensive evolutionary analysis been performed, despite evidence that the viruses are facing complex selective pressures associated with cross-species transmission. Using hybridization capture and high-throughput sequencing, we report here the full genome sequences of all the GALV strains and demonstrate that diversifying selection is acting on them, particularly in the envelope gene in functionally important domains, suggesting that host immune pressure is shaping GALV evolution. G ibbon ape leukemia virus (GALV) is an exogenous gammaretrovirus associated with hematopoietic neoplasms in captive colonies of white-handed gibbon (Hylobates lar). Five strains of GALV have been isolated from gibbons. The first was isolated from an animal with lymphocytic leukemia in a colony at the San Francisco Medical Center (strain SF) (1, 2). GALV was later isolated from gibbons displaying malignant tumors, notably an individual gibbon with granulocytic leukemia, at the Southeast Asia Treaty Organization Medical Research Laboratory in Bangkok, Thailand (strain SEATO) (3, 4), and another gibbon with lymphocytic leukemia from a colony on Hall's Island, near Bermuda (strain GALV-H) (5, 6). The Brain strain was isolated from two healthy gibbons injected with brain extracts from human patients with kuru and from an uninoculated cage mate (7). The SEATO strain has been shown to cause chronic myelogenous leukemia...

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An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo

Cited by 129 publications

References 21 publications

Mammalian Endogenous Retroviruses

Mammalian Endogenous Retroviruses

Broad-scale phylogenomics provides insights into retrovirus–host evolution

Episodic Diversifying Selection Shaped the Genomes of Gibbon Ape Leukemia Virus and Related Gammaretroviruses

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