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Viruses
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Endogenous Retrovirus Proteins and Their Functions
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Endogenous Retrovirus Proteins and Their Functions

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (1 October 2023) | Viewed by 8385

Special Issue Editor

Dr. Benoit Barbeau

E-Mail Website
Guest Editor
Co-director, Réseau Intersectoriel de Recherche en Santé de l'Université du Québec, Département des Sciences Biologiques, Centre de Recherche BioMed Université du Québec à Montréal, Montréal, QC H2X 3X8, Canada
Interests: HIV; HTLV-1; human endogenous retrovirus; syncytin; placenta; extracellular vesicle; pre-eclampsia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Even though endogenous retroviruses (ERVs) represent an important component of the genomes of several species, a substantial amount of information is lacking in terms of their diverse functions. However, for more than 20 years, it has been well established that the envelope genes encoded by ERV sequences are important contributors to the development and function of the placenta, specifically in the formation of multinucleated cell structures.

ERV envelope proteins have been studied in several mammalian species regarding their role in mammalian placenta, and the regulation of their expression has also been a focus of previous and ongoing research efforts. These proteins have been examined in terms of changes in their expression in various obstetric disorders, but have been further implicated in other cell-fusion processes and various human diseases.

The aim of this Special Issue of Viruses is to compile the newest contributions on ERV envelope proteins and known functions, as well as more recent roles. Evolutionary aspects underlying their appearance in different mammalian species, functional consideration related to placental function and their use as potential diagnostic markers towards various placental disorders represent a selection of topics that can be of relevance to the community involved in ERV research and of interest to a wider audience.

Dr. Benoit Barbeau
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • endogenous retrovirus
  • ERV envelope protein
  • receptor
  • cell fusion
  • cancer
  • pre-eclampsia
  • obstetric disorder
  • diagnosis
  • evolutionary conservation
  • gene regulation

Published Papers (5 papers)

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Research

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20 pages, 3121 KiB  
Article
Galectin-1 Modulates the Fusogenic Activity of Placental Endogenous Retroviral Envelopes
by Caroline Toudic, Maike Maurer, Guillaume St-Pierre, Yong Xiao, Norbert Bannert, Julie Lafond, Éric Rassart, Sachiko Sato and Benoit Barbeau
Viruses 2023, 15(12), 2441; https://doi.org/10.3390/v15122441 - 16 Dec 2023
Viewed by 1213
Abstract
Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other [...] Read more.
Syncytin-1 and -2 are glycoproteins encoded by human endogenous retrovirus (hERV) that, through their fusogenic properties, are needed for the formation of the placental syncytiotrophoblast. Previous studies suggested that these proteins, in addition to the EnvP(b) envelope protein, are also involved in other cell fusion events. Since galectin-1 is a β-galactoside-binding protein associated with cytotrophoblast fusion during placental development, we previously tested its effect on Syncytin-mediated cell fusion and showed that this protein differently modulates the fusogenic potential of Syncytin-1 and -2. Herein, we were interested in comparing the impact of galectin-1 on hERV envelope proteins in different cellular contexts. Using a syncytium assay, we first demonstrated that galectin-1 increased the fusion of Syncytin-2- and EnvP(b)-expressing cells. We then tested the infectivity of Syncytin-1 and -2 vs. VSV-G-pseudotyped viruses toward Cos-7 and various human cell lines. In the presence of galectin-1, infection of Syncytin-2-pseudotyped viruses augmented for all cell lines. In contrast, the impact of galectin-1 on the infectivity of Syncytin-1-pseudotyped viruses varied, being cell- and dose-dependent. In this study, we report the functional associations between three hERV envelope proteins and galectin-1, which should provide information on the fusogenic activity of these proteins in the placenta and other biological and pathological processes. Full article
(This article belongs to the Special Issue Endogenous Retrovirus Proteins and Their Functions)
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23 pages, 6538 KiB  
Article
ERVW-1 Activates ATF6-Mediated Unfolded Protein Response by Decreasing GANAB in Recent-Onset Schizophrenia
by Xing Xue, Xiulin Wu, Lijuan Liu, Lianzhong Liu and Fan Zhu
Viruses 2023, 15(6), 1298; https://doi.org/10.3390/v15061298 - 31 May 2023
Cited by 3 | Viewed by 1606
Abstract
Schizophrenia, a mental disorder, afflicts 1% of the worldwide population. The dysregulation of homeostasis in the endoplasmic reticulum (ER) has been implicated in schizophrenia. Moreover, recent studies indicate that ER stress and the unfolded protein response (UPR) are linked to this mental disorder. [...] Read more.
Schizophrenia, a mental disorder, afflicts 1% of the worldwide population. The dysregulation of homeostasis in the endoplasmic reticulum (ER) has been implicated in schizophrenia. Moreover, recent studies indicate that ER stress and the unfolded protein response (UPR) are linked to this mental disorder. Our previous research has verified that endogenous retrovirus group W member 1 envelope (ERVW-1), a risk factor for schizophrenia, is elevated in individuals with schizophrenia. Nevertheless, no literature is available regarding the underlying relationship between ER stress and ERVW-1 in schizophrenia. The aim of our research was to investigate the molecular mechanism connecting ER stress and ERVW-1 in schizophrenia. Here, we employed Gene Differential Expression Analysis to predict differentially expressed genes (DEGs) in the human prefrontal cortex of schizophrenic patients and identified aberrant expression of UPR-related genes. Subsequent research indicated that the UPR gene called XBP1 had a positive correlation with ATF6, BCL-2, and ERVW-1 in individuals with schizophrenia using Spearman correlation analysis. Furthermore, results from the enzyme-linked immunosorbent assay (ELISA) suggested increased serum protein levels of ATF6 and XBP1 in schizophrenic patients compared with healthy controls, exhibiting a strong correlation with ERVW-1 using median analysis and Mann–Whitney U analysis. However, serum GANAB levels were decreased in schizophrenic patients compared with controls and showed a significant negative correlation with ERVW-1, ATF6, and XBP1 in schizophrenic patients. Interestingly, in vitro experiments verified that ERVW-1 indeed increased ATF6 and XBP1 expression while decreasing GANAB expression. Additionally, the confocal microscope experiment suggested that ERVW-1 could impact the shape of the ER, leading to ER stress. GANAB was found to participate in ER stress regulated by ERVW-1. In conclusion, ERVW-1 induced ER stress by suppressing GANAB expression, thereby upregulating the expression of ATF6 and XBP1 and ultimately contributing to the development of schizophrenia. Full article
(This article belongs to the Special Issue Endogenous Retrovirus Proteins and Their Functions)
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14 pages, 1737 KiB  
Article
Modulation of HERV Expression by Four Different Encephalitic Arboviruses during Infection of Human Primary Astrocytes
by Fernando Luz de Castro, Otávio José Bernandes Brustolini, Victor Emmanuel Viana Geddes, Jorge Paes Barreto Marcondes de Souza, Soniza Vieira Alves-Leon, Renato Santana Aguiar and Ana Tereza Ribeiro Vasconcelos
Viruses 2022, 14(11), 2505; https://doi.org/10.3390/v14112505 - 12 Nov 2022
Cited by 2 | Viewed by 1566
Abstract
Human retroelements (HERVs) are retroviral origin sequences fixed in the human genome. HERVs induction is associated with neurogenesis, cellular development, immune activation, and neurological disorders. Arboviruses are often associated with the development of encephalitis. The interplay between these viruses and HERVs has not [...] Read more.
Human retroelements (HERVs) are retroviral origin sequences fixed in the human genome. HERVs induction is associated with neurogenesis, cellular development, immune activation, and neurological disorders. Arboviruses are often associated with the development of encephalitis. The interplay between these viruses and HERVs has not been fully elucidated. In this work, we analyzed RNAseq data derived from infected human primary astrocytes by Zika (ZikV), Mayaro (MayV), Oropouche (OroV) and Chikungunya (ChikV) viruses, and evaluated the modulation of HERVs and their nearby genes. Our data show common HERVs expression modulation by both alphaviruses, suggesting conserved evolutionary routes of transcription regulation. A total of 15 HERVs were co-modulated by the four arboviruses, including the highly upregulated HERV4_4q22. Data on the upregulation of genes nearby to these elements in ChikV, MayV and OroV infections were also obtained, and interaction networks were built. The upregulation of 14 genes common among all viruses was observed in the networks, and 93 genes between MayV and ChikV. These genes are related to cellular processes such as cellular replication, cytoskeleton, cell vesicle traffic and antiviral response. Together, our results support the role of HERVs induction in the transcription regulation process of genes during arboviral infections. Full article
(This article belongs to the Special Issue Endogenous Retrovirus Proteins and Their Functions)
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Review

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20 pages, 2231 KiB  
Review
Envelope Recombination: A Major Driver in Shaping Retroviral Diversification and Evolution within the Host Genome
by Saili Chabukswar, Nicole Grandi, Liang-Tzung Lin and Enzo Tramontano
Viruses 2023, 15(9), 1856; https://doi.org/10.3390/v15091856 - 31 Aug 2023
Cited by 1 | Viewed by 1264
Abstract
Endogenous retroviruses (ERVs) are integrated into host DNA as the result of ancient germ line infections, primarily by extinct exogenous retroviruses. Thus, vertebrates’ genomes contain thousands of ERV copies, providing a “fossil” record for ancestral retroviral diversity and its evolution within the host [...] Read more.
Endogenous retroviruses (ERVs) are integrated into host DNA as the result of ancient germ line infections, primarily by extinct exogenous retroviruses. Thus, vertebrates’ genomes contain thousands of ERV copies, providing a “fossil” record for ancestral retroviral diversity and its evolution within the host genome. Like other retroviruses, the ERV proviral sequence consists of gag, pro, pol, and env genes flanked by long terminal repeats (LTRs). Particularly, the env gene encodes for the envelope proteins that initiate the infection process by binding to the host cellular receptor(s), causing membrane fusion. For this reason, a major element in understanding ERVs’ evolutionary trajectory is the characterization of env changes over time. Most of the studies dedicated to ERVs’ env have been aimed at finding an “actual” physiological or pathological function, while few of them have focused on how these genes were once acquired and modified within the host. Once acquired into the organism, genome ERVs undergo common cellular events, including recombination. Indeed, genome recombination plays a role in ERV evolutionary dynamics. Retroviral recombination events that might have been involved in env divergence include the acquisition of env genes from distantly related retroviruses, env swapping facilitating multiple cross-species transmission over millions of years, ectopic recombination between the homologous sequences present in different positions in the chromosomes, and template switching during transcriptional events. The occurrence of these recombinational events might have aided in shaping retroviral diversification and evolution until the present day. Hence, this review describes and discusses in detail the reported recombination events involving ERV env to provide the basis for further studies in the field. Full article
(This article belongs to the Special Issue Endogenous Retrovirus Proteins and Their Functions)
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Other

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4 pages, 193 KiB  
Commentary
Microchimerism, PERV and Xenotransplantation
by Joachim Denner
Viruses 2023, 15(1), 190; https://doi.org/10.3390/v15010190 - 10 Jan 2023
Cited by 5 | Viewed by 2034
Abstract
Microchimerism is the presence of cells in an individual that have originated from a genetically distinct individual. The most common form of microchimerism is fetomaternal microchimerism, i.e., cells from a fetus pass through the placenta and establish cell lineages within the mother. Microchimerism [...] Read more.
Microchimerism is the presence of cells in an individual that have originated from a genetically distinct individual. The most common form of microchimerism is fetomaternal microchimerism, i.e., cells from a fetus pass through the placenta and establish cell lineages within the mother. Microchimerism was also described after the transplantation of human organs in human recipients. Consequently, microchimerism may also be expected in xenotransplantation using pig cells or organs. Indeed, microchimerism was described in patients after xenotransplantations as well as in non-human primates after the transplantation of pig organs. Here, for the first time, a comprehensive review of microchimerism in xenotransplantation is given. Since pig cells contain porcine endogenous retroviruses (PERVs) in their genome, the detection of proviral DNA in transplant recipients may be misinterpreted as an infection of the recipient with PERV. To prevent this, methods discriminating between infection and microchimerism are described. This knowledge will be important for the interpretation of screening results in forthcoming human xenotransplantations. Full article
(This article belongs to the Special Issue Endogenous Retrovirus Proteins and Their Functions)
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