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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 November 2014) | Viewed by 105890

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Prof. Dr. Welkin Johnson

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Biology Department Higgins 545, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA 02467, USA
Interests: retroviruses; endogenous retroviruses; HERV-K; gammaretroviruses; betaretroviruses; restriction factors; paleovirology; primate lentiviruses
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Dear Colleagues,

The genomes of living organisms are richly imbued with endogenous viral sequences, accumulated across the broad expanse of evolutionary time. While the most abundant and best studied of these are the endogenous retroviruses (ERV), we now appreciate that all manner of viruses have contributed sequences to host germline DNA. It is also clear that endogenous viral sequences can be found in organisms representing all the domains of life, from the smallest microbes to the largest plants and animals on earth. Endogenous viruses reflect the natural history of both virus and host, and are likely to have played significant roles in organismal evolution. In this Special Issue, we seek to explore all aspects of endogenous viruses, including the mechanisms and biological consequences of endogenization, the potential contributions of endogenous viruses to host evolution and ecology, and the use of endogenous loci for reconstructing the natural history of viruses and their hosts.

Prof. Dr. Welkin Johnson
Guest Editor

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Published Papers (12 papers)

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1170 KiB

Open AccessArticle

Frequent Infection of Human Cancer Xenografts with Murine Endogenous Retroviruses in Vivo

by Asif Naseer, Anne Terry, Kathryn Gilroy, Anna Kilbey, Ciorsdaidh Watts, Nancy Mackay, Margaret Bell, Susan Mason, Karen Blyth, Ewan Cameron and James C. Neil

Viruses 2015, 7(4), 2014-2029; https://0-doi-org.brum.beds.ac.uk/10.3390/v7042014 - 17 Apr 2015

Cited by 9 | Viewed by 7838

Abstract

Infection of human cancer xenografts in mice with murine leukemia viruses (MLVs) is a long-standing observation, but the likelihood of infection in vivo and its biological consequences are poorly understood. We therefore conducted a prospective study in commonly used xenograft recipient strains. From BALB/c nude mice engrafted with MCF7 human mammary carcinoma cells, we isolated a virus that was virtually identical to Bxv1, a locus encoding replication-competent xenotropic MLV (XMLV). XMLV was detected in 9/17 (53%) independently isolated explants. XMLV was not found in primary leukemias or in THP1 leukemia cells grown in Bxv1-negative NSG (NOD/SCID/γCnull) mice, although MCF7 explants harbored replication-defective MLV proviruses. To assess the significance of infection for xenograft behavior in vivo, we examined changes in growth and global transcription in MCF7 and the highly susceptible Raji Burkitt lymphoma cell line chronically infected with XMLV. Raji cells showed a stronger transcriptional response that included up-regulation of chemokines and effectors of innate antiviral immunity. In conclusion, the risk of de novo XMLV infection of xenografts is high in Bxv1 positive mice, while infection can have positive or negative effects on xenograft growth potential with significant consequences for interpretation of many xenograft studies. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessArticle

Genetic Diversity of Koala Retroviral Envelopes

by Wenqin Xu, Kristen Gorman, Jan Clement Santiago, Kristen Kluska and Maribeth V. Eiden

Viruses 2015, 7(3), 1258-1270; https://0-doi-org.brum.beds.ac.uk/10.3390/v7031258 - 17 Mar 2015

Cited by 31 | Viewed by 7415

Abstract

Genetic diversity, attributable to the low fidelity of reverse transcription, recombination and mutation, is an important feature of infectious retroviruses. Under selective pressure, such as that imposed by superinfection interference, gammaretroviruses commonly adapt their envelope proteins to use alternative receptors to overcome this entry block. The first characterized koala retroviruses KoRV subgroup A (KoRV-A) were remarkable in their absence of envelope genetic variability. Once it was determined that KoRV-A was present in all koalas in US zoos, regardless of their disease status, we sought to isolate a KoRV variant whose presence correlated with neoplastic malignancies. More than a decade after the identification of KoRV-A, we isolated a second subgroup of KoRV, KoRV-B from koalas with lymphomas. The envelope proteins of KoRV-A and KoRV-B are sufficiently divergent to confer the ability to bind and employ distinct receptors for infection. We have now obtained a number of additional KoRV envelope variants. In the present studies we report these variants, and show that they differ from KoRV-A and KoRV-B envelopes in their host range and superinfection interference properties. Thus, there appears to be considerable variation among KoRVs envelope genes suggesting genetic diversity is a factor following the KoRV-A infection process. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessArticle

Human Endogenous Retrovirus Group E and Its Involvement in Diseases

by Christelle Le Dantec, Sophie Vallet, Wesley H. Brooks and Yves Renaudineau

Viruses 2015, 7(3), 1238-1257; https://0-doi-org.brum.beds.ac.uk/10.3390/v7031238 - 16 Mar 2015

Cited by 28 | Viewed by 7631

Abstract

Human endogenous retrovirus group E (HERV-E) elements are stably integrated into the human genome, transmitted vertically in a Mendelian manner, and are endowed with transcriptional activity as alternative promoters or enhancers. Such effects are under the control of the proviral long terminal repeats (LTR) that are organized into three HERV-E phylogenetic subgroups, namely LTR2, LTR2B, and LTR2C. Moreover, HERV-E expression is tissue-specific, and silenced by epigenetic constraints that may be disrupted in cancer, autoimmunity, and human placentation. Interest in HERV-E with regard to these conditions has been stimulated further by concerns regarding the capacity of HERV-E elements to modify the expression of neighboring genes and/or to produce retroviral proteins, including immunosuppressive env peptides, which in turn may induce (auto)-antibody (Ab) production. Finally, better understanding of HERV-E elements may have clinical applications for prevention, diagnosis, prognosis, and therapy. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessArticle

Differential Expression of HERV-K (HML-2) Proviruses in Cells and Virions of the Teratocarcinoma Cell Line Tera-1

by Neeru Bhardwaj, Meagan Montesion, Farrah Roy and John M. Coffin

Viruses 2015, 7(3), 939-968; https://0-doi-org.brum.beds.ac.uk/10.3390/v7030939 - 04 Mar 2015

Cited by 49 | Viewed by 8632

Abstract

Human endogenous retrovirus (HERV-K (HML-2)) proviruses are among the few endogenous retroviral elements in the human genome that retain coding sequence. HML-2 expression has been widely associated with human disease states, including different types of cancers as well as with HIV-1 infection. Understanding of the potential impact of this expression requires that it be annotated at the proviral level. Here, we utilized the high throughput capabilities of next-generation sequencing to profile HML-2 expression at the level of individual proviruses and secreted virions in the teratocarcinoma cell line Tera-1. We identified well-defined expression patterns, with transcripts emanating primarily from two proviruses located on chromosome 22, only one of which was efficiently packaged. Interestingly, there was a preference for transcripts of recently integrated proviruses, over those from other highly expressed but older elements, to be packaged into virions. We also assessed the promoter competence of the 5’ long terminal repeats (LTRs) of expressed proviruses via a luciferase assay following transfection of Tera-1 cells. Consistent with the RNASeq results, we found that the activity of most LTRs corresponded to their transcript levels. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessArticle

ERVK Polyprotein Processing and Reverse Transcriptase Expression in Human Cell Line Models of Neurological Disease

by Mamneet Manghera, Jennifer Ferguson and Renée Douville

Viruses 2015, 7(1), 320-332; https://0-doi-org.brum.beds.ac.uk/10.3390/v7010320 - 20 Jan 2015

Cited by 28 | Viewed by 8108

Abstract

Enhanced expression of the reverse transcriptase (RT) protein encoded by human endogenous retrovirus-K (ERVK) is a promising biomarker for several inflammatory and neurological diseases. However, unlike RT enzymes encoded by exogenous retroviruses, little work has been done to identify ERVK RT isoforms, their expression patterns, and cellular localization. Using Western blot, we showcase the ERVK gag-pro-pol polyprotein processing leading to the production of several ERVK RT isoforms in human neuronal (ReNcell CX) and astrocytic (SVGA) models of neuroinflammatory disease. Since the pro-inflammatory cytokine IFNγ plays a key role in the pathology of several ERVK-associated neurological diseases, we sought to determine if IFNγ can drive ERVK RT expression. IFNγ signalling markedly enhanced ERVK polyprotein and RT expression in both human astrocytes and neurons. RT isoforms were expressed in a cell-type specific pattern and the RT-RNase H form was significantly increased with IFNγ treatment. Fluorescent imaging revealed distinct cytoplasmic, perinuclear and nuclear ERVK RT staining patterns upon IFNγ stimulation of astrocytes and neurons. These findings indicate that ERVK expression is inducible under inflammatory conditions such as IFNγ exposure—and thus, these newly established in vitro models may be useful in exploring ERVK biology in the context of neuroinflammatory disease. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Review

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1022 KiB

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The Roles of Syncytin-Like Proteins in Ruminant Placentation

by Yuki Nakaya and Takayuki Miyazawa

Viruses 2015, 7(6), 2928-2942; https://0-doi-org.brum.beds.ac.uk/10.3390/v7062753 - 05 Jun 2015

Cited by 18 | Viewed by 9882

Abstract

Recent developments in genome sequencing techniques have led to the identification of huge numbers of endogenous retroviruses (ERV) in various mammals. ERVs, which occupy 8%–13% of mammalian genomes, are believed to affect mammalian evolution and biological diversity. Although the functional significance of most ERVs remains to be elucidated, several ERVs are thought to have pivotal roles in host physiology. We and other groups recently identified ERV envelope proteins (e.g., Fematrin-1, Syncytin-Rum1, endogenous Jaagsiekte sheep retrovirus Env) that may determine the morphogenesis of the unique fused trophoblast cells, termed trinucleate cells and syncytial plaques, found in ruminant placentas; however, there are still a number of outstanding issues with regard to the role of ERVs that remain to be resolved. Here, we review what is known about how these ERVs have contributed to the development of ruminant-specific trophoblast cells. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Open AccessFeature PaperReview

Origins of the Endogenous and Infectious Laboratory Mouse Gammaretroviruses

by Christine A. Kozak

Viruses 2015, 7(1), 1-26; https://0-doi-org.brum.beds.ac.uk/10.3390/v7010001 - 26 Dec 2014

Cited by 52 | Viewed by 10301

Abstract

The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses (XRVs) and as endogenous retroviruses (ERVs) inserted into their host genomes. There are three major mouse leukemia virus (MuLV) subgroups in laboratory mice: ecotropic, xenotropic, and polytropic. These MuLV subgroups differ in host range, pathogenicity, receptor usage and subspecies of origin. The MuLV ERVs are recent acquisitions in the mouse genome as demonstrated by the presence of many full-length nondefective MuLV ERVs that produce XRVs, the segregation of these MuLV subgroups into different house mouse subspecies, and by the positional polymorphism of these loci among inbred strains and individual wild mice. While some ecotropic and xenotropic ERVs can produce XRVs directly, others, especially the pathogenic polytropic ERVs, do so only after recombinations that can involve all three ERV subgroups. Here, I describe individual MuLV ERVs found in the laboratory mice, their origins and geographic distribution in wild mouse subspecies, their varying ability to produce infectious virus and the biological consequences of this expression. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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“Ménage à Trois”: The Evolutionary Interplay between JSRV, enJSRVs and Domestic Sheep

by Alessia Armezzani, Mariana Varela, Thomas E. Spencer, Massimo Palmarini and Frédérick Arnaud

Viruses 2014, 6(12), 4926-4945; https://0-doi-org.brum.beds.ac.uk/10.3390/v6124926 - 09 Dec 2014

Cited by 29 | Viewed by 8812

Abstract

Sheep betaretroviruses represent a fascinating model to study the complex evolutionary interplay between host and pathogen in natural settings. In infected sheep, the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRV) coexists with a variety of highly related endogenous JSRVs, referred to as enJSRVs. During evolution, some of them were co-opted by the host as they fulfilled important biological functions, including placental development and protection against related exogenous retroviruses. In particular, two enJSRV loci, enJS56A1 and enJSRV-20, were positively selected during sheep domestication due to their ability to interfere with the replication of related competent retroviruses. Interestingly, viruses escaping these transdominant enJSRVs have recently emerged, probably less than 200 years ago. Overall, these findings suggest that in sheep the process of endogenization is still ongoing and, therefore, the evolutionary interplay between endogenous and exogenous sheep betaretroviruses and their host has not yet reached an equilibrium. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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In between: Gypsy in Drosophila melanogaster Reveals New Insights into Endogenous Retrovirus Evolution

by Franck Touret, François Guiguen, Timothy Greenland and Christophe Terzian

Viruses 2014, 6(12), 4914-4925; https://0-doi-org.brum.beds.ac.uk/10.3390/v6124914 - 09 Dec 2014

Cited by 5 | Viewed by 7315

Abstract

Retroviruses are RNA viruses that are able to synthesize a DNA copy of their genome and insert it into a chromosome of the host cell. Sequencing of different eukaryote genomes has revealed the presence of many such endogenous retroviral sequences. The mechanisms by which these retroviral sequences have colonized the genome are still unknown, and the endogenous retrovirus gypsy of Drosophila melanogaster is a powerful experimental model for deciphering this process in vivo. Gypsy is expressed in a layer of somatic cells, and then transferred into the oocyte by an unknown mechanism. This critical step is the start of the endogenization process. Moreover gypsy has been shown to have infectious properties, probably due to its envelope gene acquired from a baculovirus. Recently we have also shown that gypsy maternal transmission is reduced in the presence of the endosymbiotic bacterium Wolbachia. These studies demonstrate that gypsy is a unique and powerful model for understanding the endogenization of retroviruses. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Implication of Human Endogenous Retrovirus Envelope Proteins in Placental Functions

by Adjimon Gatien Lokossou, Caroline Toudic and Benoit Barbeau

Viruses 2014, 6(11), 4609-4627; https://0-doi-org.brum.beds.ac.uk/10.3390/v6114609 - 24 Nov 2014

Cited by 76 | Viewed by 12029

Abstract

Human endogenous retroviruses (ERVs) represent 8% of the total human genome. Although the majority of these ancient proviral sequences have only retained non-coding long terminal repeats (LTRs), a number of “endogenized” retroviral genes encode functional proteins. Previous studies have underlined the implication of these ERV-derived proteins in the development and the function of the placenta. In this review, we summarize recent findings showing that two ERV genes, termed Syncytin-1 and Syncytin-2, which encode former envelope (Env) proteins, trigger fusion events between villous cytotrophoblasts and the peripheral multinucleated syncytiotrophoblast layer. Such fusion events maintain the stability of this latter cell structure, which plays an important role in fetal development by the active secretion of various soluble factors, gas exchange and regulation of fetomaternal immunotolerance. We also highlight new studies showing that these ERV proteins, in addition to their localization at the cell surface of cytotrophoblasts, are also incorporated on the surface of various extracellular microvesicles, including exosomes. Such exosome-associated proteins could be involved in the various functions attributed to these vesicles and could provide a form of tropism. Additionally, through their immunosuppressive domains, these ERV proteins could also contribute to fetomaternal immunotolerance in a local and more distal manner. These various aspects of the implication of Syncytin-1 and -2 in placental function are also addressed in the context of the placenta-related disorder, preeclampsia. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Host Control of Insect Endogenous Retroviruses: Small RNA Silencing and Immune Response

by Marie Fablet

Viruses 2014, 6(11), 4447-4464; https://0-doi-org.brum.beds.ac.uk/10.3390/v6114447 - 18 Nov 2014

Cited by 10 | Viewed by 8424

Abstract

Endogenous retroviruses are relics of ancient infections from retroviruses that managed to integrate into the genome of germline cells and remained vertically transmitted from parent to progeny. Subsequent to the endogenization process, these sequences can move and multiply in the host genome, which can have deleterious consequences and disturb genomic stability. Natural selection favored the establishment of silencing pathways that protect host genomes from the activity of endogenous retroviruses. RNA silencing mechanisms are involved, which utilize piRNAs. The response to exogenous viral infections uses siRNAs, a class of small RNAs that are generated via a distinct biogenesis pathway from piRNAs. However, interplay between both pathways has been identified, and interactions with anti-bacterial and anti-fungal immune responses are also suspected. This review focuses on Diptera (Arthropods) and intends to compile pieces of evidence showing that the RNA silencing pathway of endogenous retrovirus regulation is not independent from immunity and the response to infections. This review will consider the mechanisms that allow the lasting coexistence of viral sequences and host genomes from an evolutionary perspective. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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Porcine Endogenous Retroviruses in Xenotransplantation—Molecular Aspects

by Magdalena C. Kimsa, Barbara Strzalka-Mrozik, Malgorzata W. Kimsa, Joanna Gola, Peter Nicholson, Krzysztof Lopata and Urszula Mazurek

Viruses 2014, 6(5), 2062-2083; https://0-doi-org.brum.beds.ac.uk/10.3390/v6052062 - 13 May 2014

Cited by 37 | Viewed by 8182

Abstract

In the context of the shortage of organs and other tissues for use in human transplantation, xenotransplantation procedures with material taken from pigs have come under increased consideration. However, there are unclear consequences of the potential transmission of porcine pathogens to humans. Of particular concern are porcine endogenous retroviruses (PERVs). Three subtypes of PERV have been identified, of which PERV-A and PERV-B have the ability to infect human cells in vitro. The PERV-C subtype does not show this ability but recombinant PERV-A/C forms have demonstrated infectivity in human cells. In view of the risk presented by these observations, the International Xenotransplantation Association recently indicated the existence of four strategies to prevent transmission of PERVs. This article focuses on the molecular aspects of PERV infection in xenotransplantation and reviews the techniques available for the detection of PERV DNA, RNA, reverse transcriptase activity and proteins, and anti-PERV antibodies to enable carrying out these recommendations. These methods could be used to evaluate the risk of PERV transmission in human recipients, enhance the effectiveness and reliability of monitoring procedures, and stimulate discussion on the development of improved, more sensitive methods for the detection of PERVs in the future. Full article

(This article belongs to the Special Issue Endogenous Viruses)

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