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. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals

Genome-wide characterization of endogenous retroviruses in snub-nosed monkeys

Background Endogenous retroviruses (ERV) are remnants of former exogenous retroviruses that had previously invaded the germ line of the host that can be vertically transmitted across generations. While the majority of ERVs lack infectious capacity due to the accumulation of deleterious mutations, some ERVs remain active and produce potentially infectious viral particles. ERV sequences have been reported in all mammals; however, the distribution and diversity of ERVs in several primate taxa remains unclear. The aim of this study was to identify and classify the ERV sequences in the genomes of the golden snub-nosed monkey (Rhinopithecus roxellana) and the black and white snub-nosed monkey (Rhinopithecus bieti), two endangered primate species that exploit high altitude (2,500–4,500 m) temperate forests in southern and central China. Methods We used a TBLASTN program to search the ERV sequences of golden snub-nosed monkey genome and the black and white snub-nosed monkey genome. We retrieved all complete accession sequences from the homology search and then used the program, RetroTector, to check and identify the ERV sequences. Results We identified 284 and 263 endogenous retrovirus sequences in R. roxellana and R. bieti respectively. The proportion of full-length sequences of all ERV was 30% in R. roxellana and 21% in R. bieti and they were described as class I and class II or gamma-retrovirus and beta-retrovirus genera. The truncation pattern distribution in the two species was virtually identical. By analyzing and comparing ERV orthologues among 6 primate species, we identified the co-evolution of ERVs with their host. We also examined ERV-like sequences and found 48 such genes in R. roxellana and 63 in R. bieti. Some of those genes are associated with diseases, suggesting that ERVs might have involved the abnormal expression of certain genes that have contributed to deleterious consequences for the host. Conclusions Our results indicate that ERV sequences are widely distributed in snub-nosed monkeys, and their phylogenetic history can mirror that of their hosts over long evolutionary time scales. In addition, ERV sequences appear to have an important influence on the evolution of host pathology

Long-term host–pathogen evolution of endogenous beta- and gammaretroviruses in mouse lemurs with little evidence of recent retroviral introgression

Madagascar’s flora and fauna have evolved in relative isolation since the island split from the African and Indian continents. When the last common ancestors of lemurs left Africa between 40 and 70 million years ago, they carried a subset of the viral diversity of the mainland population within them, which continued to evolve throughout the lemur radiation. Relative to other primate radiations, we know very little about the past or present viral diversity of lemurs, particularly mouse lemurs. Using high-throughput sequencing, we identified two gammaretroviruses and three betaretroviruses in the genomes of four species of wild mouse lemurs. The two gammaretroviruses and two betaretroviruses have not previously been described. One betaretrovirus was previously identified. All identified viruses are present in both Lorisiformes and Lemuriformes but absent from haplorrhine primates. The estimated ages of these viruses are consistent with the estimated divergence dates of the host lineages, suggesting they colonized the lemur genome after the Haplorrhine–Strepsirrhine split, but before the Lorisiformes–Lemuriformes split and before the colonization of Madagascar. The viral phylogenies connect multiple lineages of retroviruses from non-lemur and non-Madagascar-native species, suggesting substantial cross-species transmission occurred deep in the primate clade prior to its geographic dispersal. These phylogenies provide novel insights into known retroviral clades. They suggest that the origin of gammaretroviruses in rodents or bats may be premature and that the Jaagsiekte sheep virus clade may be older and more broadly distributed among mammals than previously thought

Identification and characterization of ERV-W-like sequences in Platyrrhini species provides new insights into the evolutionary history of ERV-W in primates

Background: Endogenous Retroviruses (ERVs) constitute approximately 8% of every human genome and are relics of ancestral infections that affected the germ line cells. The ERV-W group contributed to primate physiology by providing an envelope protein (Syncytin-1) that has been adopted for placenta development in hominoids. Expression of Human ERV-W (HERV-W) sequences is investigated for a pathological role in various human diseases. Results: We previously characterized ERV-W group genomic sequences in human and non-human Catarrhini species. We now investigated ERV-W-like sequences in the parvorder Platyrrhini, especially regarding two species with complete genome assemblies, namely marmoset (Callithrix jacchus) and squirrel monkey (Saimiri boliviensis). We identified in both species proviral sequences, annotated as ERV1-1 in respective genome assemblies, sharing high sequence similarities with Catarrhini ERV-W. A total of 130 relatively intact proviruses from the genomes of marmoset and squirrel monkey were characterized regarding their structural and evolutionarily relationships with Catarrhini ERV-W elements. Platyrrhini ERV-W sequences share several structural features with Catarrhini ERV-W elements and are closely related phylogenetically with the latter as well as with other ERV-W-related gammaretrovirus-like ERVs. The ERV-W group colonized Platyrrhini primates of both Callitrichidae and Atelidae lineages, with provirus formations having occurred mostly between 25 and 15 mya. Two LTR subgroups were associated with monophyletic proviral bodies. A pre-gag region appears to be a sequence feature common to the ERV-W group: it harbors a putative intron sequence that is missing in some ERV-W loci, holding a putative ORF as well. The presence of a long pre-gag portion was confirmed among all gammaretroviral ERV analyzed, suggesting a role in the latter biology. It is noteworthy that, contrary to Catarrhini ERV-W, there was no evidence of L1-mediated mobilization for Platyrrhini ERV-W sequences. Conclusions: Our data establish that ERV-W is not exclusive to Catarrhini primates but colonized both parvorders of Simiiformes, providing further insight into the evolution of ERV-W and the colonization of primate genomes

Murine Gammaretrovirus Group G3 Was Not Found in Swedish Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia

BACKGROUND: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans. RESULTS: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria. CONCLUSIONS: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors

Molecular analysis of dog and wolf genomic DNA to explore integration polymorphisms of Canine Endogenous Retroviruses, CfERV

Endogenous retroviruses (ERVs) are found in all examined vertebrate genomes. Different mammals have been reported to contain different amounts of ERVs. For example, in the dog genome 0.15% of sequences are derived from retroviruses. Genome rearrangements driven by retroviral transposition likely have had effects on plasticity of mammalian genomes. During evolution, occasionally, exogenous retrovirus (XRVs) infected germ line cells and the acquired provirus might have been transmitted vertically from generation to generation as a normal Mendelian trait. These rare events of germline infections will result in the generation of ERVs. To gain further insights into the nature of Canine Endogenous Retroviruses (CfERVs) we have performed a PCR-based survey of insertional polymorphism of those CfERVs that were estimated to have integrated recently due to the low degree of divergence of their respective 5’ and 3’ long terminal repeats (LTRs). The presence of potential integration polymorphism was analysed in genomic DNA prepared from different dog breeds and several wolves by using locus-specific primers for CfERV-chromosomal junctions. We did not find any evidence for integration polymorphism for the CfERV-Fc4 group, which may indicate that integration of this group of CfERVs occurred prior to domestication of dogs from Canis lupus. Furthermore, using sequence annotation tools the implication of CfERVs in canine copy-number variation (CNVs) was estimated and we have found evidences for overlap between CfERVs and CNVs

Long-term host-pathogen evolution of endogenous beta- and gammaretroviruses in mouse lemurs with little evidence of recent retroviral introgression

Madagascar’s flora and fauna have evolved in relative isolation since the island split from the African and Indian continents. When the last common ancestors of lemurs left Africa between 40 and 70 million years ago, they carried a subset of the viral diversity of the mainland population within them, which continued to evolve throughout the lemur radiation. Relative to other primate radiations, we know very little about the past or present viral diversity of lemurs, particularly mouse lemurs. Using high-throughput sequencing, we identified two gammaretroviruses and three betaretroviruses in the genomes of four species of wild mouse lemurs. The two gammaretroviruses and two betaretroviruses have not previously been described. One betaretrovirus was previously identified. All identified viruses are present in both Lorisiformes and Lemuriformes but absent from haplorrhine primates. The estimated ages of these viruses are consistent with the estimated divergence dates of the host lineages, suggesting they colonized the lemur genome after the Haplorrhine–Strepsirrhine split, but before the Lorisiformes–Lemuriformes split and before the colonization of Madagascar. The viral phylogenies connect multiple lineages of retroviruses from non-lemur and non-Madagascar-native species, suggesting substantial cross-species transmission occurred deep in the primate clade prior to its geographic dispersal. These phylogenies provide novel insights into known retroviral clades. They suggest that the origin of gammaretroviruses in rodents or bats may be premature and that the Jaagsiekte sheep virus clade may be older and more broadly distributed among mammals than previously thought

Phylogeny-Directed Search for Murine Leukemia Virus-Like Retroviruses in Vertebrate Genomes and in Patients Suffering from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Prostate Cancer

Gammaretrovirus-like sequences occur in most vertebrate genomes. Murine Leukemia Virus (MLV) like retroviruses (MLLVs) are a subset, which may be pathogenic and spread cross-species. Retroviruses highly similar to MLLVs (xenotropic murine retrovirus related virus (XMRV) and Human Mouse retrovirus-like RetroViruses (HMRVs)) reported from patients suffering from prostate cancer (PC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) raise the possibility that also humans have been infected. Structurally intact, potentially infectious MLLVs occur in the genomes of some mammals, especially mouse. Mouse MLLVs contain three major groups. One, MERV G3, contained MLVs and XMRV/HMRV. Its presence in mouse DNA, and the abundance of xenotropic MLVs in biologicals, is a source of false positivity. Theoretically, XMRV/HMRV could be one of several MLLV transspecies infections. MLLV pathobiology and diversity indicate optimal strategies for investigating XMRV/HMRV in humans and raise ethical concerns. The alternatives that XMRV/HMRV may give a hard-to-detect “stealth” infection, or that XMRV/HMRV never reached humans, have to be considered

No Definite Evidence for Human Endogenous Retroviral HERV-W and HERV-H RNAS in Plasma of Latvian Patients Suffering from Multiple Sclerosis and Other Neurological Diseases

Publisher Copyright: © 2016 by Jonas Blomberg.Multiple sclerosis (MS) is a neurological disease of unknown aetiology. Several research groups reported an increased level of human endogenous retroviruses HERV-W and HERV-H RNAs in cerebrospinal fluid, plasma and supernatants of cell cultures from MS individuals. To quantify the abundance of extracellular virion-associated HERV, RNAs in blood, plasma samples from Latvian MS patients, patients with other neurological diseases (OND), as well as blood donors (BD), were retrospectively studied by using both our previously published and newly developed quantitative Real-time reverse transcription PCR assays (QPCRs) targeting different polymerase (pol) gene regions of HERV-W and HERV-H. Unspecific signals due to incomplete removal of DNA were monitored by running the assays with and without reverse transcription (RT±) in parallel. According to our score, a few MS, OND and healthy controls gave borderline signals simultaneously with both newly developed HERV-H and HERV-W QPCRs, but the rest were negative. All borderline positive samples also had small amounts of non-retroviral cellular mRNA with possible origin from cell-free circulating RNA fragments, apoptotic bodies or exosomes, which can mimic the previously described virus-like particles. The results do not confirm the previous reports on prevalence of HERV-H or-W virion-associated RNA in plasma of MS patients.publishersversionPeer reviewe