Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis.
TL;DR: It is shown that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenousSyncytin can be inhibited by an anti-syncytin antiserum, and thus may be important in human placental morphogenesis.
Abstract: Many mammalian viruses have acquired genes from their hosts during their evolution1. The rationale for these acquisitions is usually quite clear: the captured genes are subverted to provide a selective advantage to the virus. Here we describe the opposite situation, where a viral gene has been sequestered to serve an important function in the physiology of a mammalian host. This gene, encoding a protein that we have called syncytin, is the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W2. We find that the major sites of syncytin expression are placental syncytiotrophoblasts, multinucleated cells that originate from fetal trophoblasts. We show that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibited by an anti-syncytin antiserum. Our data indicate that syncytin may mediate placental cytotrophoblast fusion in vivo, and thus may be important in human placental morphogenesis.
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TL;DR: The approach to utilizing available RNA-Seq and other data types in the authors' manual curation process for vertebrate, plant, and other species is summarized, and a new direction for prokaryotic genomes and protein name management is described.
Abstract: The RefSeq project at the National Center for Biotechnology Information (NCBI) maintains and curates a publicly available database of annotated genomic, transcript, and protein sequence records (http://www.ncbi.nlm.nih.gov/refseq/). The RefSeq project leverages the data submitted to the International Nucleotide Sequence Database Collaboration (INSDC) against a combination of computation, manual curation, and collaboration to produce a standard set of stable, non-redundant reference sequences. The RefSeq project augments these reference sequences with current knowledge including publications, functional features and informative nomenclature. The database currently represents sequences from more than 55,000 organisms (>4800 viruses, >40,000 prokaryotes and >10,000 eukaryotes; RefSeq release 71), ranging from a single record to complete genomes. This paper summarizes the current status of the viral, prokaryotic, and eukaryotic branches of the RefSeq project, reports on improvements to data access and details efforts to further expand the taxonomic representation of the collection. We also highlight diverse functional curation initiatives that support multiple uses of RefSeq data including taxonomic validation, genome annotation, comparative genomics, and clinical testing. We summarize our approach to utilizing available RNA-Seq and other data types in our manual curation process for vertebrate, plant, and other species, and describe a new direction for prokaryotic genomes and protein name management.
4,104 citations
Cites background from "Syncytin is a captive retroviral en..."
...The syncytin proteins, which are involved in placental development (28), are a well-known exception to this....
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TL;DR: In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.
1,181 citations
Cites background from "Syncytin is a captive retroviral en..."
...…produce functional proteins including group-specific antigen (gag), polymerase (pol) with reverse transcriptase (RT), and the envelope (env) surface unit (SU) with a transmembrane immunosuppressive-like peptide (Mi et al., 2000; Blaise et al., 2005; de Parseval et al., 2003; Villesen et al., 2004)....
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...Most ERV genes are non-functional due to DNA recombination, mutations, and deletions, but some produce functional proteins including group-specific antigen (gag), polymerase (pol) with reverse transcriptase (RT), and the envelope (env) surface unit (SU) with a transmembrane immunosuppressive-like peptide (Mi et al., 2000; Blaise et al., 2005; de Parseval et al., 2003; Villesen et al., 2004)....
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...…several known ERV env genes like Syncytin-1, ERV-3, env-K, and env-H (Blond et al., 1999; Löwer Cell 162, 974–986, August 27, 2015 ª2015 Elsevier Inc. 977 et al., 1993; Mi et al., 2000; Rote et al., 2004) and at especially high levels, env-Fc2, a less well-characterized gene (Bénit et al., 2003)....
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...2) called Syncytin-1 has an essential role in placentogenesis (Blond et al., 1999; Mi et al., 2000)....
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TL;DR: It is shown that a cellular microRNA effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (PFV-1) in human cells and has direct antiviral effects in addition to their regulatory functions.
Abstract: In eukaryotes, 21- to 24-nucleotide-long RNAs engage in sequence-specific interactions that inhibit gene expression by RNA silencing. This process has regulatory roles involving microRNAs and, in plants and insects, it also forms the basis of a defense mechanism directed by small interfering RNAs that derive from replicative or integrated viral genomes. We show that a cellular microRNA effectively restricts the accumulation of the retrovirus primate foamy virus type 1 (PFV-1) in human cells. PFV-1 also encodes a protein, Tas, that suppresses microRNA-directed functions in mammalian cells and displays cross-kingdom antisilencing activities. Therefore, through fortuitous recognition of foreign nucleic acids, cellular microRNAs have direct antiviral effects in addition to their regulatory functions.
943 citations
TL;DR: In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA activation, which suggests that Lingo-1 has an important role in CNS biology.
Abstract: Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These inhibitors seem to modulate RhoA activity by binding to a receptor complex comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal transducing subunit (the neurotrophin receptor p75). However, in reconstituted non-neuronal systems, NgR1 and p75 together are unable to activate RhoA, suggesting that additional components of the receptor may exist. Here we describe LINGO-1, a nervous system-specific transmembrane protein that binds NgR1 and p75 and that is an additional functional component of the NgR1/p75 signaling complex. In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA activation. A dominant-negative human LINGO-1 construct attenuated myelin inhibition in transfected primary neuronal cultures. This effect on neurons was mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together these observations suggest that LINGO-1 has an important role in CNS biology.
836 citations
TL;DR: A comprehensive transcriptional map of human embryo development, including the sequenced transcriptomes of 1,529 individual cells from 88 human preimplantation embryos, shows that cells undergo an intermediate state of co-expression of lineage-specific genes, followed by a concurrent establishment of the trophectoderm, epiblast, and primitive endoderm lineages, which coincide with blastocyst formation.
827 citations
References
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Book•
01 Jan 1991
TL;DR: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, and animal models of autoimmune and inflammatory diseases.
Abstract: Current Protocols in Immunology is a three-volume looseleaf manual that provides comprehensive coverage of immunological methods from classic to the most cutting edge, including antibody detection and preparation, assays for functional activities of mouse and human cells involved in immune responses, assays for cytokines and their receptors, isolation and analysis of proteins and peptides, biochemistry of cell activation, molecular immunology, and animal models of autoimmune and inflammatory diseases. Carefully edited, step-by-step protocols replete with material lists, expert commentaries, and safety and troubleshooting tips ensure that you can duplicate the experimental results in your own laboratory.Bimonthly updates, which are filed into the looseleaf, keep the set current with the latest developments in immunology methods.The initial purchase includes one year of updates and then subscribers may renew their annual subscriptions.Current Protocols publishes a family of laboratory manuals for bioscientists, including Molecular Biology, Human Genetics, Protein Science, Cytometry, Cell Biology, Neuroscience, Pharmacology, and Toxicology.
7,396 citations
TL;DR: In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation and suppresses T cell activity and defends itself against rejection.
Abstract: In 1953 Medawar pointed out that survival of the genetically disparate (allogeneic) mammalian conceptus contradicts the laws of tissue transplantation. Rapid T cell-induced rejection of all allogeneic concepti occurred when pregnant mice were treated with a pharmacologic inhibitor of indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing enzyme expressed by trophoblasts and macrophages. Thus, by catabolizing tryptophan, the mammalian conceptus suppresses T cell activity and defends itself against rejection.
2,499 citations
"Syncytin is a captive retroviral en..." refers background in this paper
...They are important in maternal–fetal exchange, in tissue remodelling during placental development and in protecting the developing fetus from the maternal immune respons...
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TL;DR: HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts and is present in choriocarcinoma cell lines studied.
Abstract: The alpha chain of the human histocompatibility antigen HLA-G was identified as an array of five 37- to 39-kilodalton isoforms by the use of two-dimensional gel electrophoresis. Both cell-associated and secreted HLA-G antigens are prominent in first trimester villous cytotrophoblasts and are greatly reduced in third trimester cytotrophoblasts. Allelic variation was not detected, an indication that HLA-G is not obviously polymorphic in cytotrophoblasts. Among the following choriocarcinoma cell lines studied, HLA-G is expressed in JEG but not in Jar or BeWo. Expression of endogenous HLA-G genes has not been found in normal lymphoid cells. Thus, HLA-G is subject to both cell type-specific and developmental regulation and is expressed in early gestation human cytotrophoblasts.
1,373 citations
"Syncytin is a captive retroviral en..." refers background in this paper
...1 ), and thus abundant syncytin expression in placental syncytiotrophoblasts may contribute towards immune tolerance of the developing embryo, although additional mechanisms have also been propose...
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TL;DR: The mammalian embryo cannot develop without the placenta, which binds the embryo to the uterus and redirects maternal endocrine, immune, and metabolic functions to the embryo's advantage.
Abstract: The mammalian embryo cannot develop without the placenta. Its specialized cells (trophoblast, endoderm, and extraembryonic mesoderm) form early in development. They attach the embryo to the uterus (implantation) and form vascular connections necessary for nutrient transport. In addition, the placenta redirects maternal endocrine, immune, and metabolic functions to the embryo's advantage. These complex activities are sensitive to disruption, as shown by the high incidence of early embryonic mortality and pregnancy diseases in humans, as well as the numerous peri-implantation lethal mutations in mice. Integration of molecular and developmental approaches has recently produced insights into the molecules that control these processes.
1,331 citations
"Syncytin is a captive retroviral en..." refers background in this paper
...They are important in maternal–fetal exchange, in tissue remodelling during placental development and in protecting the developing fetus from the maternal immune respons...
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TL;DR: The study of host-virus interactions provides not only a glimpse of life at immunity's edge, but it has also illuminated essential functions of the immune system, in particular, the area of major histocompatibility complex-restricted antigen presentation.
Abstract: The vertebrate body is an ideal breeding ground for viruses and provides the conditions that promote their growth, survival, and transmission. The immune system evolved and deals with this challenge. Mutually assured destruction is not a viable evolutionary strategy; thus, the study of host-virus interactions provides not only a glimpse of life at immunity's edge, but it has also illuminated essential functions of the immune system, in particular, the area of major histocompatibility complex-restricted antigen presentation.
769 citations
Additional excerpts
...gif" NDATA ITEM> ]> Many mammalian viruses have acquired genes from their hosts during their evolutio...
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