Discovery of endogenous retroviruses with mammalian envelopes in avian genomes uncovers long-term bird-mammal interaction

Mammalian genomes typically contain hundreds of thousands of endogenous retroviruses (ERVs), derived from ancient retroviral infections. Using this molecular 'fossil' record, we reconstructed the natural history of a specific retrovirus lineage (ERV-Fc) that disseminated widely between ~33 and ~15 million years ago, corresponding to the Oligocene and early Miocene epochs. Intercontinental viral spread, numerous instances of interspecies transmission and emergence in hosts representing at least 11 mammalian orders, and a significant role for recombination in diversification of this viral lineage were also revealed. By reconstructing the canonical retroviral genes, we identified patterns of adaptation consistent with selection to maintain essential viral protein functions. Our results demonstrate the unique potential of the ERV fossil record for studying the processes of viral spread and emergence as they play out across macro-evolutionary timescales, such that looking back in time may prove insightful for predicting the long-term consequences of newly emerging viral infections.

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Endogenous retroviruses drive species-specific germline transcriptomes in mammals

10.1101/2020.03.11.987230 ◽

2020 ◽

Author(s):

Akihiko Sakashita ◽

So Maezawa ◽

Kris G. Alavattam ◽

Masashi Yukawa ◽

Artem Barski ◽

...

Keyword(s):

Gene Activation ◽

Endogenous Retroviruses ◽

Evolutionary Divergence ◽

Binding Motifs ◽

Genome Wide ◽

Germline Genes ◽

Human Spermatogenesis ◽

Species Specific ◽

Accessible Chromatin

AbstractGene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species, and speciation. Germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition in males and have been subject to evolutionary divergence among mammals. However, the mechanism that underlies germline regulatory divergence remains undetermined. Here, we show that endogenous retroviruses influence species-specific germline transcriptomes in mammals. We show that the expression of endogenous retroviruses, particularly the evolutionarily young K family (ERVK), is associated with gene activation after the mitosis-to-meiosis transition in male mice. We demonstrate that accessible chromatin and H3K27ac, a marker of active enhancers, are tightly associated with ERVK loci as well as with the activation of neighboring evolutionarily young germline genes. Thus, ERVKs serve as evolutionarily novel enhancers in mouse spermatogenesis. These ERVK loci bear binding motifs for critical regulators of spermatogenesis such as A-MYB. The genome-wide transposition of ERVKs might have rewired germline gene expression in a species-specific manner. Notably, these features are present in human spermatogenesis, but independently evolved ERVs are associated with expression of germline genes, demonstrating the prevalence of ERV-driven mechanisms in mammals. Together, we propose a model whereby species-specific transcriptomes are fine-tuned by endogenous retroviruses in the mammalian germline.

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Distribution, Diversity, and Evolution of Endogenous Retroviruses in Perissodactyl Genomes

Journal of Virology ◽

10.1128/jvi.00927-18 ◽

2018 ◽

Vol 92 (23) ◽

Author(s):

Henan Zhu ◽

Robert James Gifford ◽

Pablo Ramiro Murcia

Keyword(s):

Germ Line ◽

Mammalian Species ◽

Endogenous Retroviruses ◽

Functional Roles ◽

Physiological Processes ◽

Great Utility ◽

White Rhinoceros ◽

History Of ◽

Mammalian Genomes

ABSTRACTThe evolution of mammalian genomes has been shaped by interactions with endogenous retroviruses (ERVs). In this study, we investigated the distribution and diversity of ERVs in the mammalian orderPerissodactyla, with a view to understanding their impact on the evolution of modern equids (familyEquidae). We characterize the major ERV lineages in the horse genome in terms of their genomic distribution, ancestral genome organization, and time of activity. Our results show that subsequent to their ancestral divergence from rhinoceroses and tapirs, equids acquired four novel ERV lineages. We show that two of these ERV lineages proliferated extensively in the lineage leading to modern horses, and one contains loci that are actively transcribed in specific tissues. In addition, we show that the white rhinoceros has resisted germ line colonization by retroviruses for more than 54 million years—longer than any other extant mammalian species. The map of equine ERVs that we provide here will be of great utility to future studies aiming to investigate the potential functional roles of equine ERVs and their impact on equine evolution.IMPORTANCEERVs in the host genome are highly informative about the long-term interactions of retroviruses and hosts. They are also interesting because they have influenced the evolution of mammalian genomes in various ways. In this study, we derive a calibrated timeline describing the process through which ERV diversity has been generated in the equine germ line. We determined the distribution and diversity of perissodactyl ERV lineages and inferred their retrotranspositional activity during evolution, thereby gaining insight into the long-term coevolutionary history of retroviruses and mammals. Our study provides a platform for future investigations to identify equine ERV loci involved in physiological processes and/or pathological conditions.

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Is there a role for endogenous retroviruses to mediate long-term adaptive phenotypic response upon environmental inputs?

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2011.0340 ◽

2013 ◽

Vol 368 (1609) ◽

pp. 20110340 ◽

Cited By ~ 19

Author(s):

Jafar Sharif ◽

Yoichi Shinkai ◽

Haruhiko Koseki

Keyword(s):

Gene Regulation ◽

Endogenous Retroviruses ◽

Highly Active ◽

Global Gene Regulation ◽

Mammalian Genomes ◽

Insertion Sites ◽

Genomic Locations ◽

The Impact ◽

Evolutionary Role

Endogenous retroviruses (ERVs) are long terminal repeat-containing virus-like elements that have colonized approximately 10 per cent of the present day mammalian genomes. The intracisternal A particles (IAPs) are a class of ERVs that is currently highly active in the rodents. IAP elements can influence the transcription profile of nearby genes by providing functional promoter elements and modulating local epigenetic landscape through changes in DNA methylation and histone (H3K9) modifications. Despite the potential role for IAPs in gene regulation, the precise genomic locations where these elements are integrated are not well understood. To address this issue, we have identified more than 400 novel IAP insertion sites within/near annotated genes by searching the murine genome, which suggests that the impact of IAP elements on local and/or global gene regulation could be more profound than was previously expected. On the basis of our independent analyses and already published reports, here we argue that IAPs and ERV elements in general could have an evolutionary role for modulating phenotypic plasticity upon environmental inputs, and that this could be mediated through specific stages of embryonic development such as placentation during which the epigenetic constraints on IAP elements are partially relaxed.

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Modeling Borna Disease Virus In Vitro Spread Reveals the Mode of Antiviral Effect Conferred by an Endogenous Bornavirus-Like Element

Journal of Virology ◽

10.1128/jvi.01204-20 ◽

2020 ◽

Vol 94 (21) ◽

Author(s):

Kwang Su Kim ◽

Yusuke Yamamoto ◽

Shinji Nakaoka ◽

Keizo Tomonaga ◽

Shingo Iwami ◽

...

Keyword(s):

Antiviral Activity ◽

Disease Virus ◽

Virus Replication ◽

Ground Squirrel ◽

Cultured Cells ◽

Antiviral Effect ◽

Endogenous Retroviruses ◽

Virus Spread ◽

Borna Disease

ABSTRACT Endogenous retroviruses have demonstrated exaptation during long-term evolution with hosts, e.g., resulting in acquisition of antiviral effect on related extant viral infections. While empirical studies have found that an endogenous bornavirus-like element derived from viral nucleoprotein (itEBLN) in the ground squirrel genome shows antiviral effect on virus replication and de novo infection, the antiviral mechanism, dynamics, and quantitative effect of itEBLN remain unknown. In this study, we experimentally and theoretically investigated the dynamics of how an extant bornavirus, Borna disease virus 1 (BoDV-1), spreads and replicates in uninfected, BoDV-1-infected, and itEBLN-expressing cultured cells. Quantifying antiviral effect based on time course data sets, we found that the antiviral effects of itEBLN are estimated to be 75% and 34% on intercellular virus spread and intracellular virus replication, respectively. This discrepancy between intercellular virus spread and intracellular viral replication suggests that viral processes other than the replication of viral ribonucleoprotein complex (RNP) contributed to the suppression of virus spread in itEBLN-expressing cells. Because itEBLN binds to the BoDV-1 RNP, the suppression of viral RNP trafficking can be an attractive candidate explaining this discrepancy. IMPORTANCE Accumulating evidence suggests that some endogenous viral elements (EVEs), including endogenous retroviruses and endogenous nonretroviral virus elements, have acquired functions in the host as a result of long-term coevolution. Recently, an endogenous bornavirus-like element (itEBLN) found in the ground squirrel genome has been shown to have antiviral activity against exogenous bornavirus infection. In this study, we first quantified bornavirus spread in cultured cells and then calculated the antiviral activity of itEBLN on bornavirus infection. The calculated antiviral activity of itEBLN suggests its suppression of multiple processes in the viral life cycle. To our knowledge, this is the first study quantifying the antiviral activity of EVEs and speculating on a model of how some EVEs have acquired antiviral activity during host-virus arms races.

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Identification and evolution of avian endogenous foamy viruses

Virus Evolution ◽

10.1093/ve/vez049 ◽

2019 ◽

Vol 5 (2) ◽

Cited By ~ 1

Author(s):

Yicong Chen ◽

Xiaoman Wei ◽

Guojie Zhang ◽

Edward C Holmes ◽

Jie Cui

Keyword(s):

Bird Species ◽

Single Origin ◽

Foamy Viruses ◽

History Of ◽

Flanking Sequences ◽

Animal Hosts ◽

Ideal Framework ◽

Host Evolution ◽

Avian Genomes

Abstract A history of long-term co-divergence means that foamy viruses (family Retroviridae) provide an ideal framework to understanding virus-host evolution over extended time periods. Endogenous foamy viruses (EndFVs) are rare, and to date have only been described in a limited number of mammals, amphibians, reptiles and fish genomes. By screening 414 avian genomes we identified EndFVs in two bird species: the Maguari Stork (Ciconia maguari) and the Oriental Stork (Ciconia boyciana). Analyses of phylogenetic relationships, genome structures and flanking sequences revealed a single origin of EndFVs in Ciconia species. In addition, the marked incongruence between the virus and host phylogenies suggested that this integration event occurred independently in birds. In sum, by providing evidence that birds can be infected with foamy viruses, we fill the last major gap in the taxonomic distribution of foamy viruses and their animal hosts.

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Movements of ancient human endogenous retroviruses detected in SOX2-expressing cells

10.1101/2020.07.14.202135 ◽

2020 ◽

Author(s):

Kazuaki Monde ◽

Yorifumi Satou ◽

Mizuki Goto ◽

Yoshikazu Uchiyama ◽

Jumpei Ito ◽

...

Keyword(s):

Stem Cells ◽

Somatic Cells ◽

Endogenous Retroviruses ◽

Genome Integrity ◽

Human Endogenous Retroviruses ◽

Early Embryos ◽

Integration Sites ◽

Induced Pluripotent ◽

Harmful Effects

SummaryHuman endogenous retroviruses (HERVs) occupy approximately 8% of human genome. HERVs, which are transcribed in early embryos, are epigenetically silenced in somatic cells, except in pathological contexts. HERV-K is thought to protect the embryo from exogenous viral infection. However, uncontrollable HERV-K expression in somatic cells has been implicated in several diseases. Here, we show that SOX2, which plays a key role in maintaining pluripotency of stem cells, is critical for the transcription of HERV-K LTR5Hs. HERV-K can undergo retrotransposition within producer cells in the absence of Env expression. Furthermore, new HERV-K integration sites were identified in a long-term culture of induced pluripotent stem cells, which express SOX2. Together, these results suggest the possibility that the strict dependence of HERV-K on SOX2 have allowed contribution of HERV-K to the protection of early embryos during evolution while limiting potentially harmful effects of HERV-K retrotransposition on host genome integrity to these early embryos.

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Long-term reinfection of the human genome by endogenous retroviruses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0307800101 ◽

2004 ◽

Vol 101 (14) ◽

pp. 4894-4899 ◽

Cited By ~ 214

Author(s):

R. Belshaw ◽

V. Pereira ◽

A. Katzourakis ◽

G. Talbot ◽

J. Paces ◽

...

Keyword(s):

Human Genome ◽

Endogenous Retroviruses

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Retroviruses drive the rapid evolution of mammalianAPOBEC3genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1914183116 ◽

2019 ◽

Vol 117 (1) ◽

pp. 610-618 ◽

Cited By ~ 15

Author(s):

Jumpei Ito ◽

Robert J. Gifford ◽

Kei Sato

Keyword(s):

Gene Family ◽

Fossil Record ◽

Driving Force ◽

Mammalian Species ◽

Rapid Evolution ◽

Endogenous Retroviruses ◽

Mammalian Evolution ◽

History Of ◽

Mammalian Genomes

APOBEC3(A3) genes are members of theAID/APOBECgene family that are found exclusively in mammals.A3genes encode antiviral proteins that restrict the replication of retroviruses by inducing G-to-A mutations in their genomes and have undergone extensive amplification and diversification during mammalian evolution. Endogenous retroviruses (ERVs) are sequences derived from ancient retroviruses that are widespread mammalian genomes. In this study we characterize theA3repertoire and use the ERV fossil record to explore the long-term history of coevolutionary interaction between A3s and retroviruses. We examine the genomes of 160 mammalian species and identify 1,420AID/APOBEC-related genes, including representatives of previously uncharacterized lineages. We show thatA3genes have been amplified in mammals and that amplification is positively correlated with the extent of germline colonization by ERVs. Moreover, we demonstrate that the signatures of A3-mediated mutation can be detected in ERVs found throughout mammalian genomes and show that in mammalian species with expandedA3repertoires, ERVs are significantly enriched for G-to-A mutations. Finally, we show thatA3amplification occurred concurrently with prominent ERV invasions in primates. Our findings establish that conflict with retroviruses is a major driving force for the rapid evolution of mammalianA3genes.

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Identification and evolution of avian endogenous foamy viruses

10.1101/707083 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yicong Chen ◽

Xiaoman Wei ◽

Guojie Zhang ◽

Edward C. Holmes ◽

Jie Cui

Keyword(s):

Bird Species ◽

Single Origin ◽

Foamy Viruses ◽

History Of ◽

Flanking Sequences ◽

Animal Hosts ◽

Ideal Framework ◽

Host Evolution ◽

Avian Genomes

AbstractA history of long-term co-divergence means that foamy viruses (family Retroviridae) provide an ideal framework to understanding virus-host evolution over extended time periods. Endogenous foamy viruses (EndFVs) are rare, and to date have only been described in a limited number of mammals, amphibians, reptiles and fish genomes. By screening 414 avian genomes we identified EndFVs in two bird species: the Maguari Stork (Ciconia maguari) and the Oriental Stork (C. boyciana). Analyses of phylogenetic relationships, genome structures and flanking sequences revealed a single origin of EndFVs in Ciconia species. In addition, the marked incongruence between the virus and host phylogenies suggested that this integration event occurred independently in birds. In sum, by providing evidence that birds can be infected with foamy viruses, we fill the last major gap in the taxonomic distribution of foamy viruses and their animal hosts.

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