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 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 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 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 On transposons and totipotency

2020 ◽  
Vol 375 (1795) ◽  
pp. 20190339 ◽  
Author(s):  
Maria-Elena Torres-Padilla
Keyword(s):  
Large Scale ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Host Genome ◽  
The Past ◽  
Stage Of Development ◽  
Mammalian Genomes

Our perception of the role of the previously considered ‘selfish’ or ‘junk’ DNA has been dramatically altered in the past 20 years or so. A large proportion of this non-coding part of mammalian genomes is repetitive in nature, classified as either satellites or transposons. While repetitive elements can be termed selfish in terms of their amplification, such events have surely been co-opted by the host, suggesting by itself a likely altruistic function for the organism at the subject of such natural selection. Indeed numerous examples of transposons regulating the functional output of the host genome have been documented. Transposons provide a powerful framework for large-scale relatively rapid concerted regulatory activities with the ability to drive evolution. Mammalian totipotency has emerged as one key stage of development in which transposon-mediated regulation of gene expression has taken centre stage in the past few years. During this period, large-scale (epigenetic) reprogramming must be accomplished in order to activate the host genome. In mice and men, one particular element murine endogenous retrovirus with leucine tRNA primer (MERVL) (and its counterpart human ERVL (HERVL)) appears to have acquired roles as a key driving force in this process. Here, I will discuss and interpret the current knowledge and its implications regarding the role of transposons, particularly of long interspersed nuclear elements (LINE-1s) and endogenous retroviruses (ERVs), in the regulation of totipotency. This article is part of a discussion meeting issue ‘Crossroads between transposons and gene regulation’.

scholarly journals Characterization of the Long Terminal Repeat of the Endogenous Retrovirus-derived microRNAs in the Olive Flounder

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hee-Eun Lee ◽  
Ara Jo ◽  
Jennifer Im ◽  
Hee-Jae Cha ◽  
Woo-Jin Kim ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Long Terminal Repeat ◽  
Sequence Similarity ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Terminal Repeat ◽  
Chromosome 9 ◽  
Olive Flounder ◽  
High Sequence Similarity ◽  
Enhancer Activity

Abstract Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3′ untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.

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 evolutionary history of a gammaretrovirus currently colonizing the mule deer genome is marked by extensive recombination

2021 ◽  
Author(s):  
Lei Yang ◽  
Raunaq Malhotra ◽  
Rayan Chikhi ◽  
Daniel Elleder ◽  
Theodora Kaiser ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Mule Deer ◽  
Endogenous Retrovirus ◽  
Host Population ◽  
Endogenous Retroviruses ◽  
Genomic Diversity ◽  
Evolutionary Trajectory ◽  
History Of

AbstractBackgroundAll vertebrate genomes have been colonized by retroviruses along their evolutionary trajectory. Although it is clear that endogenous retroviruses (ERVs) can contribute important physiological functions to contemporary hosts, such benefits are attributed to long-term co-evolution of ERV and host. Newly colonized ERVs are thought unlikely to contribute to host genome evolution because germline infections are rare and because the host effectively silences them. The genomes of several outbred species including mule deer (Odocoileus hemionus) are currently being colonized by ERVs, which provides an opportunity to study ERV dynamics at a time when few are fixed.Here we investigate the history of cervid endogenous retrovirus (CrERV) acquisition and expansion in the mule deer genome to determine the potential impact of endogenizing retroviruses on host genomic diversity.MethodsA mule deer genome was de novo assembled from short and long insert mate pair reads. Scaffolds were further assembled using reference assisted chromosome assembly (RACA) to provide spatial orientation of CrERV insertion sites and to facilitate assembly of CrERV sequences. We applied phylogenetic and coalescent approaches to non-recombinant genomes to determine CrERV evolutionary history, augmenting ancestral divergence estimates with the prevalence of each CrERV locus in a population of mule deer. Recombination history was investigated on partial genome alignments.ResultsThe CrERV composition and diversity in the mule deer genome has recently measurably increased by horizontal acquisition of a new retroviruses lineage and because of recombination with existing CrERV. Resulting interlineage recombinants also endogenized and subsequently retrotransposed. CrERV loci are significantly closer to genes than expected if integration were random and gene proximity might explain the recent expansion by retrotransposition of one recombinant CrERV lineage.ConclusionsThere has been a burst of CrERV integrations during a recent retrovirus epizootic that increased genomic CrERV burden and has resulted in extensive insertional polymorphism in contemporary mule deer genomes. Recombination is a defining feature of CrERV evolutionary dynamics driven by this colonization, increasing CrERV burden and CrERV genetic diversity. These data support that retroviral colonization during an epizootic provides a burst of genomic diversity to the host population.

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 Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations

2018 ◽  
Vol 115 (43) ◽  
pp. 11012-11017 ◽  
Author(s):  
Salvador Daniel Rivas-Carrillo ◽  
Mats E. Pettersson ◽  
Carl-Johan Rubin ◽  
Patric Jern
Keyword(s):  
Nuclear Dna ◽  
Endogenous Retrovirus ◽  
Host Population ◽  
Endogenous Retroviruses ◽  
European Rabbit ◽  
Genome Comparison ◽  
Whole Genome ◽  
Genome Data ◽  
Host Phylogeny ◽  
Domestic Rabbits

Although recent advances in sequencing and computational analyses have facilitated use of endogenous retroviruses (ERVs) for deciphering coevolution among retroviruses and their hosts, sampling effects from different host populations present major challenges. Here we utilize available whole-genome data from wild and domesticated European rabbit (Oryctolagus cuniculus sp.) populations, sequenced as DNA pools by paired-end Illumina technology, for identifying segregating reference as well as nonreference ERV loci, to reveal their variation along the host phylogeny and domestication history. To produce new viruses, retroviruses must insert a proviral DNA copy into the host nuclear DNA. Occasional proviral insertions into the host germline have been passed down through generations as inherited ERVs during millions of years. These ERVs represent retroviruses that were active at the time of infection and thus present a remarkable record of historical virus–host associations. To examine segregating ERVs in host populations, we apply a reference library search strategy for anchoring ERV-associated short-sequence read pairs from pooled whole-genome sequences to reference genome assembly positions. We show that most ERVs segregate along host phylogeny but also uncover radiation of some ERVs, identified as segregating loci among wild and domestic rabbits. The study targets pertinent issues regarding genome sampling when examining virus–host evolution from the genomic ERV record and offers improved scope regarding common strategies for single-nucleotide variant analyses in host population comparative genomics.

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.

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