scholarly journals Cross-species transmission and differential fate of an endogenous retrovirus in three mammal lineages

2015 ◽  
Author(s):  
Xiaoyu Zhuo ◽  
Cedric Feschotte
Keyword(s):  
Mammalian Species ◽  
Extended Period ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Myotis Lucifugus ◽  
Multiple Infection ◽  
Deep Time ◽  
Genome Sequence Database ◽  
Species Specific ◽  
Retroviral Infections

Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmission events. Here we took advantage of a catalog of ERVs we recently produced for the bat Myotis lucifugus to seek evidence for infiltration of these retroviruses in other mammalian species (>100) currently represented in the genome sequence database. We provide multiple lines of evidence for the cross-ordinal transmission of a gammaretrovirus endogenized independently in the lineages of vespertilionid bats, felid cats and pangolin ~13-25 million years ago. Following its initial introduction, the ERV amplified extensively in parallel in both bat and cat lineages, generating hundreds of species-specific insertions throughout evolution. However, despite being derived from the same viral species, phylogenetic and selection analyses suggest that the ERV experienced different amplification dynamics in the two mammalian lineages. In the cat lineage, the ERV appears to have expanded primarily by retrotransposition of a single proviral progenitor that lost infectious capacity shortly after endogenization. In the bat lineage, the ERV followed a more complex path of germline invasion characterized by both retrotransposition and multiple infection events. The results also suggest that some of the bat ERVs have maintained infectious capacity for extended period of time and may be still infectious today. This study provides one of the most rigorously documented cases of cross-ordinal transmission of a mammalian retrovirus. It also illustrates how the same retrovirus species has transitioned multiple times from an infectious pathogen to a genomic parasite (i.e. retrotransposon), yet experiencing different invasion dynamics in different mammalian hosts.

scholarly journals Mobilization of Endogenous Retroviruses in Mice after Infection with an Exogenous Retrovirus

2008 ◽  
Vol 83 (6) ◽  
pp. 2429-2435 ◽  
Author(s):  
Leonard H. Evans ◽  
A. S. M. Alamgir ◽  
Nick Owens ◽  
Nick Weber ◽  
Kimmo Virtaneva ◽  
...  
Keyword(s):  
Germ Line ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Gene Sequences ◽  
Endogenous Viruses ◽  
Mammalian Genomes ◽  
Leukemia Viruses ◽  
Retroviral Infections ◽  
Ecotropic Virus ◽  
Rna Transcript

ABSTRACT Mammalian genomes harbor a large number of retroviral elements acquired as germ line insertions during evolution. Although many of the endogenous retroviruses are defective, several contain one or more intact viral genes that are expressed under certain physiological or pathological conditions. This is true of the endogenous polytropic retroviruses that generate recombinant polytropic murine leukemia viruses (MuLVs). In these recombinants the env gene sequences of exogenous ecotropic MuLVs are replaced with env gene sequences from an endogenous polytropic retrovirus. Although replication-competent endogenous polytropic retroviruses have not been observed, the recombinant polytropic viruses are capable of replicating in numerous species. Recombination occurs during reverse transcription of a virion RNA heterodimer comprised of an RNA transcript from an endogenous polytropic virus and an RNA transcript from an exogenous ecotropic MuLV RNA. It is possible that homodimers corresponding to two full-length endogenous RNA genomes are also packaged. Thus, infection by an exogenous virus may result not only in recombination with endogenous sequences, but also in the mobilization of complete endogenous retrovirus genomes via pseudotyping within exogenous retroviral virions. We report that the infection of mice with an ecotropic virus results in pseudotyping of intact endogenous viruses that have not undergone recombination. The endogenous retroviruses infect and are integrated into target cell genomes and subsequently replicate and spread as pseudotyped viruses. The mobilization of endogenous retroviruses upon infection with an exogenous retrovirus may represent a major interaction of exogenous retroviruses with endogenous retroviruses and may have profound effects on the pathogenicity of retroviral infections.

scholarly journals Identification of Novel Porcine Endogenous Betaretrovirus Sequences in Miniature Swine

2001 ◽  
Vol 75 (6) ◽  
pp. 2765-2770 ◽  
Author(s):  
Thomas Ericsson ◽  
Beth Oldmixon ◽  
Jonas Blomberg ◽  
Margaret Rosa ◽  
Clive Patience ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Fetal Liver ◽  
Phylogenetic Analyses ◽  
Mammalian Species ◽  
Peripheral Blood Lymphocytes ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Miniature Swine ◽  
Porcine Endogenous Retrovirus

ABSTRACT PCR amplification of genomic DNA from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely related to betaretroviruses. The identification of PERVs belonging to theBetaretrovirus genus shows that endogenous retroviruses of this family are more broadly represented in mammalian species than previously appreciated. Both sequences contained inactivating mutations, implying that these particular loci are defective. However, Southern blot analysis showed additional copies of closely related proviruses in the miniature swine genome. Analyses of fetal and adult miniature swine tissues revealed a broad mRNA expression pattern of both PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow c-kit +(CD117+) progenitor bone marrow cells, fetal liver, salivary gland, and thymus. It appears unlikely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The betaretrovirus sequences described in this report will allow such investigations to be actively pursued.

scholarly journals Hypermutation of an Ancient Human Retrovirus by APOBEC3G

2008 ◽  
Vol 82 (17) ◽  
pp. 8762-8770 ◽  
Author(s):  
Young Nam Lee ◽  
Michael H. Malim ◽  
Paul D. Bieniasz
Keyword(s):  
Human Genome ◽  
Cytidine Deaminase ◽  
Modern Human ◽  
Endogenous Retrovirus ◽  
Human Infection ◽  
Endogenous Retroviruses ◽  
Host Interactions ◽  
Apobec3 Proteins ◽  
Retroviral Infections

ABSTRACT Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome, but all are remnants of ancient retroviral infections and harbor inactivating mutations that render them replication defective. Nevertheless, as viral “fossils,” HERVs may provide insights into ancient retrovirus-host interactions and their evolution. Indeed, one endogenous retrovirus [HERV-K(HML-2)], which has replicated in humans for the past few million years but is now thought to be extinct, was recently reconstituted in a functional form, and infection assays based on it have been established. Here, we show that several human APOBEC3 proteins are intrinsically capable of mutating and inhibiting infection by HERV-K(HML-2) in cell culture. We also present striking evidence that two HERV-K(HML-2) proviruses that are fixed in the modern human genome (HERV-K60 and HERV-KI) were subjected to hypermutation by a cytidine deaminase. Inspection of the spectrum of mutations that are found in HERV-K proviruses in the human genome and HERV-K DNA generated during in vitro replication in the presence of each of the human APOBEC3 proteins unequivocally identifies APOBEC3G as the cytidine deaminase responsible for hypermutation of HERV-K60 and HERV-KI. This is a rare example of the antiretroviral effects of APOBEC3G in the setting of natural human infection, whose consequences have been fossilized in human DNA, and a striking example of inactivation of ancient retroviruses in humans through enzymatic cytidine deamination.

scholarly journals Mechanisms of Late Restriction Induced by an Endogenous Retrovirus

2007 ◽  
Vol 81 (20) ◽  
pp. 11441-11451 ◽  
Author(s):  
Frederick Arnaud ◽  
Pablo R. Murcia ◽  
Massimo Palmarini
Keyword(s):  
Endogenous Retrovirus ◽  
Dominant Negative ◽  
Endogenous Retroviruses ◽  
Restriction Factors ◽  
Recycling Endosome ◽  
Recycling Endosomes ◽  
Viral Particles ◽  
Bona Fide ◽  
Retroviral Infections ◽  
Late Stages

ABSTRACT The host has developed during evolution a variety of “restriction factors” to fight retroviral infections. We investigated the mechanisms of a unique viral block acting at late stages of the retrovirus replication cycle. The sheep genome is colonized by several copies of endogenous retroviruses, known as enJSRVs, which are highly related to the oncogenic jaagsiekte sheep retrovirus (JSRV). enJS56A1, one of the enJSRV proviruses, can act as a restriction factor by blocking viral particles release of the exogenous JSRV. We show that in the absence of enJS56A1 expression, the JSRV Gag (the retroviral internal structural polyprotein) targets initially the pericentriolar region, in a dynein and microtubule-dependent fashion, and then colocalizes with the recycling endosomes. Indeed, by inhibiting the endocytosis and trafficking of recycling endosomes we hampered JSRV exit from the cell. Using a variety of approaches, we show that enJS56A1 and JSRV Gag interact soon after synthesis and before pericentriolar/recycling endosome targeting of the latter. The transdominant enJS56A1 induces intracellular Gag accumulation in microaggregates that colocalize with the aggresome marker GFP-250 but develop into bona fide aggresomes only when the proteasomal machinery is inhibited. The data argue that dominant-negative proteins can modify the overall structure of Gag multimers/viral particles hampering the interaction of the latter with the cellular trafficking machinery.

scholarly journals The identification and classification of endogenous retroviruses in the horse genome

2018 ◽  
Vol 23 (01) ◽  
pp. 3-8
Author(s):  
Batmagnai E ◽  
Erik Bongcam-Rudloff ◽  
Matthew Peter Kent ◽  
Göran Andersson
Keyword(s):  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Open Reading Frames ◽  
Degenerate Primers ◽  
Online Tool ◽  
Horse Genome ◽  
Control Functions ◽  
Retroviral Infections ◽  
Host Genes

Endogenous retroviruses (ervs) are sequences that derived from ancient retroviral infections of germ cells and integrated in humans, mammals and other vertebrates millions years ago. These ervs are inherited according to Mendelian expectations as all other genes in the genome. Coding sequences are flanked by two ltrs (long terminal repeat sequences). Most ervs are defective however some ervs still have open reading frames in their genome. These ervs settle close to functional genes or within the genes and can influence or control functions of the host genes using their ltrs. Most integration has deleterious effects. However some integration could be example of positive co-adaptation as syncitin. The first equine endogenous beta retrovirus which is ecerv-beta1 has been found in 2011 by Antoinette C.van der Kuyl1. The first known beta retrovirus and few pol gene similar to foamy retrovirus were only known endogenous retroviruses fixed in the domestic horse (equuscaballus) genome. Our aim of the study was to identify other endogenous retrovirus sequences in an equine genome and classify them into groups. Based on the high number of sines (equine repetitive element) in the horse genome we hypothesized that certain ervs will be located sufficiently close to sines that they will be amplified using an unbiased sine-pcr approach with degenerate primers. The nearest sine element was located 5.5 kbp upstream at the 5’of the ecerv-beta1. Pan-pol pcr was also used to find novel ervs based on 640 bp long region of pol gene which is the most conserved region of ervs. 27 complete and novel ervs that are 13 beta, 13 gamma, 1 spuma and 249 candidate endogenous retroviruses have been revealed using ltr_struc tool and double checked by retrotector online tool and ncbi-blast tool. It was proven that ecerv-beta1, which has 2 ltrs with 1% divergence between ltrs has a polymorphism among 13 different breeds.

scholarly journals Exploring the effects of immunity and life history on the dynamics of an endogenous retrovirus

2013 ◽  
Vol 368 (1626) ◽  
pp. 20120505 ◽  
Author(s):  
R. K. Kanda ◽  
M. Tristem ◽  
T. Coulson
Keyword(s):  
Life History ◽  
Long Terminal Repeat ◽  
Humoral Immunity ◽  
Endogenous Retrovirus ◽  
Host Population ◽  
Endogenous Retroviruses ◽  
Host Genome ◽  
Final Model ◽  
Host Life ◽  
Retroviral Infections

Mammalian DNA is littered with the signatures of past retroviral infections. For example, at least 8% of the human genome can be attributed to endogenous retroviruses (ERVs). We take a single-locus approach to develop a simple susceptible–infected–recovered model to investigate the circumstances under which a disease-causing retrovirus can become incorporated into the host genome and spread through the host population if it were to confer an immunological advantage. In the absence of any fitness benefit provided by the long terminal repeat (LTR), we conclude that signatures of ERVs are likely to go to fixation within a population when the probability of evolving cellular/humoral immunity to a related exogenous version of the virus is extremely small. We extend this model to examine whether changing the speed of the host life history influences the likelihood that an exogenous retrovirus will incorporate and spread to fixation. Our results reveal the parameter space under which incorporation of exogenous retroviruses into a host genome may be beneficial to the host. In our final model, we find that the likelihood of an LTR reaching fixation in a host population is not strongly affected by host life history.

scholarly journals Endogenous Retrovirus-Derived lnc-ALVE1-AS1 Exerts Antiviral Defense Against ALV-J Infection in Chicken Macrophages

2021 ◽  
Author(s):  
Huan Luo ◽  
Xuming Hu ◽  
Huixian Wu ◽  
Gul Zaib ◽  
Wenxian Chai ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Type I Interferons ◽  
Type I ◽  
Antiviral Defense ◽  
Antiviral Innate Immunity ◽  
Retroviral Infections ◽  
Avian Leukosis Virus Subgroup ◽  
Chicken Embryo Fibroblasts

Abstract Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections dating back many millions of years, and their derived transcripts with viral signatures are important sources of long noncoding RNAs (lncRNAs). We have previously shown that the chicken ERV-derived lncRNA lnc-ALVE1-AS1 exerts antiviral innate immunity in chicken embryo fibroblasts. However, it is not clear whether this endogenous retroviral RNA has a similar function in immune cells. Here, we found that lnc-ALVE1-AS1 was persistently inhibited in chicken macrophages after avian leukosis virus subgroup J (ALV-J) infection. Furthermore, overexpression of lnc-ALVE1-AS1 significantly inhibited the proliferation of exogenous ALV-J, whereas knockdown of lnc-ALVE1-AS1 promoted the proliferation of ALV-J in chicken macrophages. This phenomenon is attributed to the induction of antiviral innate immunity by lnc-ALVE1-AS1 in macrophages, whereas knockdown of lnc-ALVE1-AS1 had the opposite effect. Mechanistically, lnc-ALVE1-AS1 can be sensed by the cytosolic pattern recognition receptor TLR3 and trigger the type I interferons response. The present study provides novel insights into the antiviral defense of ERV-derived lncRNAs in macrophages and offers new strategies for future antiviral solutions.

scholarly journals Lack of antibody response in pigs immunized with the transmembrane envelope protein of porcine endogenous retroviruses

2014 ◽  
Vol 95 (8) ◽  
pp. 1827-1831 ◽  
Author(s):  
Martina Keller ◽  
Björn Petersen ◽  
Heiner Niemann ◽  
Joachim Denner
Keyword(s):  
Neutralizing Antibodies ◽  
Mammalian Species ◽  
Neutralization Assay ◽  
Endogenous Retrovirus ◽  
Proximal Region ◽  
Endogenous Retroviruses ◽  
Placental Development ◽  
Porcine Endogenous Retrovirus ◽  
Porcine Endogenous Retroviruses ◽  
Protein P15e

Recently, we immunized different mammalian species (goats, mice, rats, rabbits, guinea pigs and hamsters) with the recombinant ectodomain of the transmembrane envelope (TM) protein p15E of porcine endogenous retrovirus (PERV). In all cases, neutralizing immune sera were induced, which recognized epitopes in the fusion peptide proximal region and the membrane proximal external region of p15E. In order to analyse whether pigs are also able to produce such antibodies, and whether such antibodies can be used to study the involvement of the TM protein in placental development (as was shown for endogenous retroviruses of other species), German landrace pigs were immunized with PERV p15E. No binding and neutralizing antibodies were produced as shown in three Western blot analyses and in a neutralization assay, indicating that pigs are tolerant to their endogenous retroviruses, at least for the ectodomain of the TM protein.

scholarly journals Modeling human brain tumours in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets

2020 ◽  
Author(s):  
Uswa Shahzad ◽  
Michael S Taccone ◽  
Sachin A Kumar ◽  
Hidehiro Okura ◽  
Stacey Krumholtz ◽  
...  
Keyword(s):  
Brain Tumours ◽  
Mammalian Species ◽  
Scientific Investigation ◽  
Screening Tools ◽  
Murine Models ◽  
Molecular Processes ◽  
C Elegans ◽  
Human Brain Tumours ◽  
Species Specific ◽  
Cancer Studies

Abstract For decades, cell biologists and cancer researchers have taken advantage of non-murine species to increase our understanding of the molecular processes that drive normal cell and tissue development, and when perturbed, cause cancer. The advent of whole genome sequencing has revealed the high genetic homology of these organisms to humans. Seminal studies in non-murine organisms such as D. melanogaster, C. elegans, and D. rerio identified many of the signaling pathways involved in cancer. Studies in these organisms offer distinct advantages over mammalian cell or murine systems. Compared to murine models, these three species have shorter lifespans, are less resource intense, and are amenable to high-throughput drug and RNA interference screening to test a myriad of promising drugs against novel targets. In this review, we introduce species specific breeding strategies, highlight the advantages of modeling brain tumours in each non-mammalian species, and underscore the successes attributed to scientific investigation using these models. We conclude with an optimistic proposal that discoveries in the fields of cancer research, and in particular neuro-oncology, may be expedited using these powerful screening tools and strategies.

scholarly journals Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1999
Author(s):  
Annacarmen Petrizzo ◽  
Concetta Ragone ◽  
Beatrice Cavalluzzo ◽  
Angela Mauriello ◽  
Carmen Manolio ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Genetic Material ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Danger Signal ◽  
Human Endogenous Retroviruses ◽  
Double Stranded Rna ◽  
Specific Antigens ◽  
Viral Mimicry

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a “danger signal” by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs). Alternatively, HERV reactivation is associated with the expression of long noncoding RNAs (lncRNAs). In this review, we will highlight recent findings on HERV reactivation in cancer and its implications for cancer immunotherapy.

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