ArticleProceedings of the National Academy of Sciences of the United States of America2007
Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 1 of them a synthesis that pooled it.
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Who cites it
172 citing papers in PubMed, 1 synthesis or guideline pooled it, 312 citations in OpenAlex.
- A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches.International journal of molecular sciences · 2022Pooled it
- The Transmembrane Envelope Protein of Porcine Endogenous Retroviruses Modulates Cytokine Release and Gene Expression in Human Immune Cells.International journal of molecular sciences · 2026Article
- Evolutionary co-option of endogenous retroviruses: syncytins as regulators of placental development and disease.Molecular biology reports · 2026Review
- An ancient alpharetrovirus lineage in bats: Evolutionary insights and possible roles in reproduction.PLoS genetics · 2026Article
- Review
- Beyond Genetic Conservation: The Baton Pass Model of Essential Biological Functions.Biomolecules · 2026Review
- Dynamics of Human Endogenous Retroviruses Expression, Proviral Load and Systemic Inflammatory Status Modulated by Physical Exercise and Aging.International journal of molecular sciences · 2026Article
- Further Evidence for the Immunosuppressive Activity of Transmembrane Envelope Protein p15E of Porcine Endogenous Retrovirus.International journal of molecular sciences · 2026Article
- Article
- Human endogenous retrovirus profiling reveals heterogenous expression in cutaneous melanoma.Frontiers in oncology · 2026Article
- HERV-K TM Subunit Elicits CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype.Frontiers in medicine · 2026Article
- Endogenous retroviruses and response to immune checkpoint inhibitors: mechanisms, clinical evidence, and therapeutic implications.Frontiers in immunology · 2026Review
- Alterations of placental HERV expression as a result of gestational COVID-19 disease.Frontiers in microbiology · 2026Article
- The expression, regulation, and function of human endogenous retroviruses in genitourinary cancers.Cell death discovery · 2025Review
- Mechanisms of Cell-Cell Fusion in SARS-CoV-2: An Evolving Strategy for Transmission and Immune Evasion.Viruses · 2025Review
- Human endogenous retrovirus ERVK3-1 characterizes a metabolically active and immunosuppressive subtype of liver cancer.Virology journal · 2025Article
- Combination Therapy Approaches to Enhance the Efficacy of ERV-Targeting Vaccines in Cancer.Cancer immunology research · 2025Review
- Birth of protein-coding exons by ancient domestication of LINE-1 retrotransposon.Genome research · 2025Article
- Transcriptional Upregulation of HERV-Viruses · 2025Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have previously demonstrated that the envelope proteins of a murine and primate retrovirus are immunosuppressive in vivo. This property was manifested by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to have the env-expressing cells escape (at least transiently) immune rejection. Here, we analyzed the immunosuppressive activity of the human and murine syncytins. These are envelope genes from endogenous retroviruses independently coopted by ancestral hosts, conserved in evolution, specifically expressed in the placenta, and with a cell-cell fusogenic activity likely contributing to placenta morphogenesis. We show that in both humans and mice, one of the two syncytins (human syncytin-2 and mouse syncytin-B) is immunosuppressive and, rather unexpectedly, the other (human syncytin-1 and mouse syncytin-A) is not (albeit able to induce cell-cell fusion). Delineation of the immunosuppressive domain by deletion analysis, combined with a comparison between immunosuppressive and nonimmunosuppressive sequences, allowed us to derive a mutation rule targeted to specific amino acids, resulting in selective switch from immunosuppressive to nonimmunosuppressive envelope proteins and vice versa. These results unravel a critical function of retroviral envelopes, not necessarily "individually" selected for in the retrovirus endogenization process, albeit "tandemly" conserved in evolution for the syncytin pairs in primates and Muridae. Selective inactivation of immunosuppression, under conditions not affecting fusogenicity, should be important for understanding the role of this function in placental physiology and maternofetal tolerance.
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