A novel class III endogenous retrovirus with a class I envelope gene in African frogs with an intact genome and developmentally regulated transcripts in Xenopus tropicalis

Abstract Background Retroviruses exist as exogenous infectious agents and as endogenous retroviruses (ERVs) integrated into host chromosomes. Such endogenous retroviruses (ERVs) are grouped into three classes roughly corresponding to the seven genera of infectious retroviruses: class I (gamma-, epsilonretroviruses), class II (alpha-, beta-, delta-, lentiretroviruses) and class III (spumaretroviruses). Some ERVs have counterparts among the known infectious retroviruses, while others represent paleovirological relics of extinct or undiscovered retroviruses. Results Here we identify an intact ERV in the Anuran amphibian, Xenopus tropicalis. XtERV-S has open reading frames (ORFs) for gag, pol (polymerase) and env (envelope) genes, with a small additional ORF in pol and a serine tRNA primer binding site. It has unusual features and domain relationships to known retroviruses. Analyses based on phylogeny and functional motifs establish that XtERV-S gag and pol genes are related to the ancient env-less class III ERV-L family but the surface subunit of env is unrelated to known retroviruses while its transmembrane subunit is class I-like. LTR constructs show transcriptional activity, and XtERV-S transcripts are detected in embryos after the maternal to zygotic mid-blastula transition and before the late tailbud stage. Tagged Gag protein shows typical subcellular localization. The presence of ORFs in all three protein-coding regions along with identical 5’ and 3’ LTRs (long terminal repeats) indicate this is a very recent germline acquisition. There are older, full-length, nonorthologous, defective copies in Xenopus laevis and the distantly related African bullfrog, Pyxicephalus adspersus. Additional older, internally deleted copies in X. tropicalis carry a 300 bp LTR substitution. Conclusions XtERV-S represents a genera-spanning member of the largely env-less class III ERV that has ancient and modern copies in Anurans. This provirus has an env ORF with a surface subunit unrelated to known retroviruses and a transmembrane subunit related to class I gammaretroviruses in sequence and organization, and is expressed in early embryogenesis. Additional XtERV-S-related but defective copies are present in X. tropicalis and other African frog taxa. XtERV-S is an unusual class III ERV variant, and it may represent an important transitional retroviral form that has been spreading in African frogs for tens of millions of years.

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Human Endogenous Retrovirus Family HERV-K(HML-5): Status, Evolution, and Reconstruction of an Ancient Betaretrovirus in the Human Genome

Journal of Virology ◽

10.1128/jvi.78.16.8788-8798.2004 ◽

2004 ◽

Vol 78 (16) ◽

pp. 8788-8798 ◽

Cited By ~ 32

Author(s):

Laurence Lavie ◽

Patrik Medstrand ◽

Werner Schempp ◽

Eckart Meese ◽

Jens Mayer

Keyword(s):

Human Genome ◽

Germ Line ◽

Consensus Sequence ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Open Reading Frames ◽

Primer Binding Site ◽

Human Endogenous Retrovirus ◽

New World Primates ◽

Human Endogenous Retroviruses

ABSTRACT The human genome harbors numerous distinct families of so-called human endogenous retroviruses (HERV) which are remnants of exogenous retroviruses that entered the germ line millions of years ago. We describe here the hitherto little-characterized betaretrovirus HERV-K(HML-5) family (named HERVK22 in Repbase) in greater detail. Out of 139 proviruses, only a few loci represent full-length proviruses, and many lack gag protease and/or env gene regions. We generated a consensus sequence from multiple alignment of 62 HML-5 loci that displays open reading frames for the four major retroviral proteins. Four HML-5 long terminal repeat (LTR) subfamilies were identified that are associated with monophyletic proviral bodies, implying different evolution of HML-5 LTRs and genes. Sequence analysis indicated that the proviruses formed approximately 55 million years ago. Accordingly, HML-5 proviral sequences were detected in Old World and New World primates but not in prosimians. No recent activity is associated with this HERV family. We also conclude that the HML-5 consensus sequence primer binding site is identical to methionine tRNA. Therefore, the family should be designated HERV-M. Our study provides important insights into the structure and evolution of the oldest betaretrovirus in the primate genome known to date.

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Molecular Characterization and Placental Expression of HERV-W, a New Human Endogenous Retrovirus Family

Journal of Virology ◽

10.1128/jvi.73.2.1175-1185.1999 ◽

1999 ◽

Vol 73 (2) ◽

pp. 1175-1185 ◽

Cited By ~ 216

Author(s):

Jean-Luc Blond ◽

Frédéric Besème ◽

Laurent Duret ◽

Olivier Bouton ◽

Frédéric Bedin ◽

...

Keyword(s):

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Open Reading Frames ◽

Primer Binding Site ◽

Human Endogenous Retrovirus ◽

Cdna Clones ◽

Human Endogenous Retroviruses ◽

Herv Family ◽

Flanking Sequences ◽

Reading Frames

ABSTRACT The multiple sclerosis-associated retrovirus (MSRV) isolated from plasma of MS patients was found to be phylogenetically and experimentally related to human endogenous retroviruses (HERVs). To characterize the MSRV-related HERV family and to test the hypothesis of a replication-competent HERV, we have investigated the expression of MSRV-related sequences in healthy tissues. The expression of MSRV-related transcripts restricted to the placenta led to the isolation of overlapping cDNA clones from a cDNA library. These cDNAs spanned a 7.6-kb region containing gag, pol, and env genes; RU5 and U3R flanking sequences; a polypurine tract; and a primer binding site (PBS). As this PBS showed similarity to avian retrovirus PBSs used by tRNATrp, this new HERV family was named HERV-W. Several genomic elements were identified, one of them containing a complete HERV-W unit, spanning all cDNA clones. Elements of this multicopy family were not replication competent, asgag and pol open reading frames (ORFs) were interrupted by frameshifts and stop codons. A complete ORF putatively coding for an envelope protein was found both on the HERV-W DNA prototype and within an RU5-env-U3R polyadenylated cDNA clone. Placental expression of 8-, 3.1-, and 1.3-kb transcripts was observed, and a putative splicing strategy was described. The apparently tissue-restricted HERV-W long terminal repeat expression is discussed with respect to physiological and pathological contexts.

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Identification and Characterization of Novel Human Endogenous Retrovirus Families by Phylogenetic Screening of the Human Genome Mapping Project Database

Journal of Virology ◽

10.1128/jvi.74.8.3715-3730.2000 ◽

2000 ◽

Vol 74 (8) ◽

pp. 3715-3730 ◽

Cited By ~ 202

Author(s):

Michael Tristem

Keyword(s):

Human Genome ◽

Genome Mapping ◽

Sequence Data ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Sequence Information ◽

Class Iii ◽

Genome Mapping Project ◽

Human Genome Mapping Project

ABSTRACT Human endogenous retroviruses (HERVs) were first identified almost 20 years ago, and since then numerous families have been described. It has, however, been difficult to obtain a good estimate of both the total number of independently derived families and their relationship to each other as well as to other members of the familyRetroviridae. In this study, I used sequence data derived from over 150 novel HERVs, obtained from the Human Genome Mapping Project database, and a variety of recently identified nonhuman retroviruses to classify the HERVs into 22 independently acquired families. Of these, 17 families were loosely assigned to the class I HERVs, 3 to the class II HERVs and 2 to the class III HERVs. Many of these families have been identified previously, but six are described here for the first time and another four, for which only partial sequence information was previously available, were further characterized. Members of each of the 10 families are defective, and calculation of their integration dates suggested that most of them are likely to have been present within the human lineage since it diverged from the Old World monkeys more than 25 million years ago.

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Characterization of Endogenous Retroviruses in Sheep

Journal of Virology ◽

10.1128/jvi.77.20.11268-11273.2003 ◽

2003 ◽

Vol 77 (20) ◽

pp. 11268-11273 ◽

Cited By ~ 14

Author(s):

Nikolai Klymiuk ◽

Mathias Müller ◽

Gottfried Brem ◽

Bernhard Aigner

Keyword(s):

Endogenous Retrovirus ◽

Ovis Aries ◽

Endogenous Retroviruses ◽

Open Reading Frames ◽

In Vivo Experiments ◽

Pregnant Sheep ◽

Reading Frames

ABSTRACT Endogenous retrovirus (ERV) sequences have been found in all mammals. In vitro and in vivo experiments revealed ERV activation and cross-species infection in several species. Sheep (Ovis aries) are used for various biotechnological purposes; however, they have not yet been comprehensively screened for ERV sequences. Therefore, the aim of the study was to classify the ERV sequences in the ovine genome (OERV) by analyzing the retroviral pro-pol sequences. Three OERV β families and nine OERV γ families were revealed. Novel open reading frames (ORF) in the amplified proviral fragment were found in one OERV β family and two OERV γ families. Hybrid OERV produced by putative recombination events were not detected. Quantitative analysis of the OERV sequences in the ovine genome revealed no relevant variations in the endogenous retroviral loads of different breeds. Expression analysis of different tissues from fetal and pregnant sheep detected mRNA from both gammaretrovirus families, showing ORF fragments. Thus, the release of retroviruses from sheep cells cannot be excluded.

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Human Endogenous Retrovirus HERV-K14 Families: Status, Variants, Evolution, and Mobilization of Other Cellular Sequences

Journal of Virology ◽

10.1128/jvi.79.5.2941-2949.2005 ◽

2005 ◽

Vol 79 (5) ◽

pp. 2941-2949 ◽

Cited By ~ 20

Author(s):

Aline Flockerzi ◽

Stefan Burkhardt ◽

Werner Schempp ◽

Eckart Meese ◽

Jens Mayer

Keyword(s):

Human Genome ◽

Germ Line ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Long Terminal Repeats ◽

Essential Information ◽

Human Endogenous Retroviruses ◽

Consensus Sequences

ABSTRACT The human genome harbors many distinct families of human endogenous retroviruses (HERVs) that stem from exogenous retroviruses that infected the germ line millions of years ago. Many HERV families remain to be investigated. We report in the present study the detailed characterization of the HERV-K14I and HERV-K14CI families as they are represented in the human genome. Most of the 68 HERV-K14I and 23 HERV-K14CI proviruses are severely mutated, frequently displaying uniform deletions of retroviral genes and long terminal repeats (LTRs). Both HERV families entered the germ line ∼39 million years ago, as evidenced by homologous sequences in hominoids and Old World primates and calculation of evolutionary ages based on a molecular clock. Proviruses of both families were formed during a brief period. A majority of HERV-K14CI proviruses on the Y chromosome mimic a higher evolutionary age, showing that LTR-LTR divergence data can indicate false ages. Fully translatable consensus sequences encoding major retroviral proteins were generated. Most HERV-K14I loci lack an env gene and are structurally reminiscent of LTR retrotransposons. A minority of HERV-K14I variants display an env gene. HERV-K14I proviruses are associated with three distinct LTR families, while HERV-K14CI is associated with a single LTR family. Hybrid proviruses consisting of HERV-K14I and HERV-W sequences that appear to have produced provirus progeny in the genome were detected. Several HERV-K14I proviruses harbor TRPC6 mRNA portions, exemplifying mobilization of cellular transcripts by HERVs. Our analysis contributes essential information on two more HERV families and on the biology of HERV sequences in general.

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An endogenous retrovirus presumed to have been endogenized or relocated recently in a marsupial, the red-necked wallaby

Genome ◽

10.1139/gen-2021-0047 ◽

2022 ◽

Author(s):

Sakura Hayashi ◽

Konami Shimizu ◽

Yusuke Honda ◽

Yukako Katsura ◽

Akihiko Koga

Keyword(s):

Endogenous Retrovirus ◽

Amino Acid Sequences ◽

Open Reading Frames ◽

Length Variation ◽

Wild Type ◽

Long Terminal Repeats ◽

Recent Event ◽

Melanin Biosynthesis ◽

Dna Fragment ◽

Reading Frames

An albino infant wallaby was born to a mother with the wild-type body color. PCR and sequencing analyses of TYR (encoding tyrosinase, which is essential for melanin biosynthesis) of this albino wallaby revealed a 7.1-kb-long DNA fragment inserted in the first exon. Because the fragment carried long terminal repeats, we assumed it to be a copy of an endogenous retrovirus, which we named walb. We cloned other walb copies residing in the genomes of this species and another wallaby species. The copies exhibited length variation, and the longest copy (>8.0 kb) contained open reading frames whose deduced amino acid sequences were well aligned with those of gag, pol, and env of retroviruses. It is not known through which of the following likely processes the walb copy was inserted into TYR: endogenization (infection of a germline cell by an exogenous virus), reinfection (infection by a virus produced from a previously endogenized provirus), or retrotransposition (intracellular relocation of a provirus). In any case, the insertion into TYR is considered to have been a recent event on an evolutionary timescale because albino mutant alleles generally do not persist for long because of their deleterious effects in wild circumstances.

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Targeting endogenous retrovirus gene transcription in human cancers

10.1101/449686 ◽

2018 ◽

Cited By ~ 1

Author(s):

Audrey T. Lin ◽

Cindy G. Santander ◽

Emanuele Marchi ◽

Timokratis Karamitros ◽

Aris Katzourakis ◽

...

Keyword(s):

Sequence Data ◽

Sequence Similarity ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Open Reading Frames ◽

Computational Method ◽

The Cancer Genome Atlas ◽

Preimplantation Embryos ◽

Cell Stage ◽

Oncogenic Pathways

AbstractEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections that make up to 8% of the human genome. Although these elements are mostly fragmented and inactive, many proviruses belonging to the HERV-K (HML-2) family, the only lineage still proliferating in the genome after the human-chimpanzee split, have intact open reading frames, some encoding for accessory genes callednp9andrecthat interact with oncogenic pathways. Many studies have established that the transient expression of ERVs are in both stem cells and cancers results in aberrant self-renewal and uncontrolled proliferation.The wealth of high-quality genomic and transcriptomic Illumina sequence data available from The Cancer Genome Atlas (TCGA) that are sequenced from a diversity of different tumour types makes it a valuable resource in cancer research. However, there is currently no universal computational method for inferring expression of specific repetitive elements from RNA-seq data, such as genes encoded by HERV-K (HML-2).This study presents a novel and a highly specific pipeline that is able to capture and measure transcription ofnp9andrecencoded by proviruses that share great sequence similarity, and are transcribed at very low levels. We show by using our novel methodology thatnp9andrecare overexpressed in breast cancer, germ cell tumours, skin melanoma, lymphoma, ovarian cancer, and prostate cancer compared to non-diseased tissues. We also show thatnp9andrecare specifically expressed in the 8 and 16-cell stage in human preimplantation embryos.

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Identification and Characterization of Two Closely Related Unclassifiable Endogenous Retroviruses in Pythons (Python molurus and Python curtus)

Journal of Virology ◽

10.1128/jvi.76.15.7607-7615.2002 ◽

2002 ◽

Vol 76 (15) ◽

pp. 7607-7615 ◽

Cited By ~ 38

Author(s):

Jon B. Huder ◽

Jürg Böni ◽

Jean-Michel Hatt ◽

Guido Soldati ◽

Hans Lutz ◽

...

Keyword(s):

Mononuclear Cells ◽

Endogenous Retrovirus ◽

Endogenous Retroviruses ◽

Open Reading Frames ◽

Peripheral Blood Mononuclear ◽

Python Regius ◽

Boa Constrictor ◽

Inclusion Body Disease ◽

Python Molurus

ABSTRACT Boid inclusion body disease (BIBD) is a fatal disorder of boid snakes that is suspected to be caused by a retrovirus. In order to identify this agent, leukocyte cultures (established from Python molurus specimens with symptoms of BIBD or kept together with such diseased animals) were assessed for reverse transcriptase (RT) activity. Virus from cultures exhibiting high RT activity was banded on sucrose density gradients, and the RT peak fraction was subjected to highly efficient procedures for the identification of unknown particle-associated retroviral RNA. A 7-kb full retroviral sequence was identified, cloned, and sequenced. This virus contained intact open reading frames (ORFs) for gag, pro, pol, and env, as well as another ORF of unknown function within pol. Phylogenetic analysis showed that the virus is distantly related to viruses from both the B and D types and the mammalian C type but cannot be classified. It is present as a highly expressed endogenous retrovirus in all P. molurus individuals; a closely related, but much less expressed virus was found in all tested Python curtus individuals. All other boid snakes tested, including Python regius, Python reticulatus, Boa constrictor, Eunectes notaeus, and Morelia spilota, were virus negative, independent of whether they had BIBD or not. Virus isolated from P. molurus could not be transmitted to the peripheral blood mononuclear cells of B. constrictor or P. regius. Thus, there is no indication that this novel virus, which we propose to name python endogenous retrovirus (PyERV), is causally linked with BIBD.

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Structure and Phylogenetic Analysis of an Endogenous Retrovirus Inserted into the Human Growth Factor Gene Pleiotrophin

Journal of Virology ◽

10.1128/jvi.72.7.6065-6072.1998 ◽

1998 ◽

Vol 72 (7) ◽

pp. 6065-6072 ◽

Cited By ~ 20

Author(s):

Anke M. Schulte ◽

Anton Wellstein

Keyword(s):

Rhesus Monkeys ◽

Human Growth ◽

Endogenous Retrovirus ◽

Primer Binding Site ◽

Human Endogenous Retrovirus ◽

Long Terminal Repeats ◽

Reading Frame ◽

Growth Factor Gene ◽

Trna Primer ◽

Type C

ABSTRACT A human endogenous retrovirus-like element (HERV), flanked by long terminal repeats of 502 and 495 nucleotides is inserted into the human pleiotrophin (PTN) gene upstream of the open reading frame. Based on its Glu-tRNA primer binding site specificity and the location within the PTN gene, we named this element HERV-E.PTN. HERV-E.PTN appears to be a recombined viral element based on its high homology (70 to 86%) in distinct areas to members of two distantly related HERV type C families, HERV-E and retrovirus-like element I (RTVL-I). Furthermore, its pseudogene region is organized from 5′ to 3′ into gag-,pol-, env-, pol-,env-similar sequences. Interestingly, full-length and partial HERV-E.PTN-homologous sequences were found in the human X chromosome, the human hereditary haemochromatosis region, and the BRCA1 pseudogene. Finally, Southern analyses indicate that the HERV-E.PTN element is present in the PTN gene of humans, chimpanzees, and gorillas but not of rhesus monkeys, suggesting that genomic insertion occurred after the separation of monkeys and apes about 25 million years ago.

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Study of Full-Length Porcine Endogenous Retrovirus Genomes with Envelope Gene Polymorphism in a Specific-Pathogen-Free Large White Swine Herd

Journal of Virology ◽

10.1128/jvi.74.18.8575-8581.2000 ◽

2000 ◽

Vol 74 (18) ◽

pp. 8575-8581 ◽

Cited By ~ 52

Author(s):

Steffi Bösch ◽

Claire Arnauld ◽

André Jestin

Keyword(s):

Endogenous Retrovirus ◽

Amino Acid Sequences ◽

Full Length ◽

Endogenous Retroviruses ◽

Envelope Gene ◽

Specific Pathogen Free ◽

Large White ◽

Porcine Endogenous Retrovirus ◽

Specific Pathogen

ABSTRACT Specific-pathogen-free (SPF) swine appear to be the most appropriate candidate for pig to human xenotransplantation. Still, the risk of endogenous retrovirus transmission represents a major obstacle, since two human-tropic porcine endogenous retroviruses (PERVs) had been characterized in vitro (P. Le Tissier, J. P. Stoye, Y. Takeuchi, C. Patience, and R. A. Weiss, Nature 389:681–682, 1997). Here we addressed the question of PERV distribution in a French Large White SPF pig herd in vivo. First, PCR screening for previously described PERV envelope genes envA, envB, and envC(D. E. Akiyoshi, M. Denaro, H. Zhu, J. L. Greenstein, P. Banerjee, and J. A. Fishman, J. Virol. 72:4503–4507, 1998; Le Tissier et al., op. cit.). demonstrated ubiquity of envAand envB sequences, whereas envC genes were absent in some animals. On this basis, selective out-breeding of pigs of remote origin might be a means to reduce proviral load in organ donors. Second, we investigated PERV genome carriage inenvC negative swine. Eleven distinct full-length PERV transcripts were isolated. The sequence of the complete envelope open reading frame was determined. The deduced amino acid sequences revealed the existence of four clones with functional and five clones with defective PERV PK-15 A- and B-like envelope sequences. The occurrence of easily detectable levels of PERV variants in different pig tissues in vivo heightens the need to assess PERV transmission in xenotransplantation animal models.

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