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      Exaptation of Retroviral Syncytin for Development of Syncytialized Placenta, Its Limited Homology to the SARS-CoV-2 Spike Protein and Arguments against Disturbing Narrative in the Context of COVID-19 Vaccination

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          Abstract

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          The anti-vaccination movement claims an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin, which plays a role in human placentation and the SARS-CoV-2 spike protein. We argue that because of very low sequence similarity between human syncytin-1 and the SARS-CoV-2 S protein, it is unlikely that any S protein-specific SARS-CoV-2 vaccine would generate an immune response which would affect fertility and pregnancy. However, further evaluation of potential impacts of COVID-19 vaccines on fertility, placentation, pregnancy and general health of mother and newborn is required.

          Abstract

          Human placenta formation relies on the interaction between fused trophoblast cells of the embryo with uterine endometrium. The fusion between trophoblast cells, first into cytotrophoblast and then into syncytiotrophoblast, is facilitated by the fusogenic protein syncytin. Syncytin derives from an envelope glycoprotein (ENV) of retroviral origin. In exogenous retroviruses, the envelope glycoproteins coded by env genes allow fusion of the viral envelope with the host cell membrane and entry of the virus into a host cell. During mammalian evolution, the env genes have been repeatedly, and independently, captured by various mammalian species to facilitate the formation of the placenta. Such a shift in the function of a gene, or a trait, for a different purpose during evolution is called an exaptation (co-option). We discuss the structure and origin of the placenta, the fusogenic and non-fusogenic functions of syncytin, and the mechanism of cell fusion. We also comment on an alleged danger of the COVID-19 vaccine based on the presupposed similarity between syncytin and the SARS-CoV-2 spike protein.

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          Most cited references75

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          Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

          How SARS-CoV-2 binds to human cells Scientists are racing to learn the secrets of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), which is the cause of the pandemic disease COVID-19. The first step in viral entry is the binding of the viral trimeric spike protein to the human receptor angiotensin-converting enzyme 2 (ACE2). Yan et al. present the structure of human ACE2 in complex with a membrane protein that it chaperones, B0AT1. In the context of this complex, ACE2 is a dimer. A further structure shows how the receptor binding domain of SARS-CoV-2 interacts with ACE2 and suggests that it is possible that two trimeric spike proteins bind to an ACE2 dimer. The structures provide a basis for the development of therapeutics targeting this crucial interaction. Science, this issue p. 1444
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            Viral targets for vaccines against COVID-19

            Vaccines are urgently needed to control the coronavirus disease 2019 (COVID-19) pandemic and to help the return to pre-pandemic normalcy. A great many vaccine candidates are being developed, several of which have completed late-stage clinical trials and are reporting positive results. In this Progress article, we discuss which viral elements are used in COVID-19 vaccine candidates, why they might act as good targets for the immune system and the implications for protective immunity.
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              Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis.

              S Mi, X. Lee, X. Li (2000)
              Many mammalian viruses have acquired genes from their hosts during their evolution. 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-W. 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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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                19 March 2021
                March 2021
                : 10
                : 3
                : 238
                Affiliations
                [1 ]Houston Methodist Research Institute, Houston, TX 77030, USA; auosef@ 123456houstonmethodist.org (A.U.); rmghobrial@ 123456houstonmethodist.org (R.M.G.)
                [2 ]Department of Surgery, Houston Methodist Hospital, Houston, TX 77030, USA
                [3 ]MD Anderson Cancer Center, Department of Genetics, University of Texas, Houston, TX 77030, USA
                [4 ]Department of Regenerative Medicine and Cell Biology, Military Institute of Hygiene and Epidemiology (WIHE), 01-163 Warsaw, Poland; jacek.kubiak@ 123456univ-rennes1.fr
                [5 ]Cell Cycle Group, Faculty of Medicine, Institute of Genetics and Development of Rennes (IGDR), University Rennes, CNRS, UMR 6290, 35043 Rennes, France
                Author notes
                Author information
                https://orcid.org/0000-0002-5192-8584
                https://orcid.org/0000-0003-2772-5127
                Article
                biology-10-00238
                10.3390/biology10030238
                8003504
                33808658
                fe2b829b-4fa7-4c89-b96e-9d899ff78bb6
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 January 2021
                : 17 March 2021
                Categories
                Review

                placenta,syncytin,spike protein,retrovirus,sars-cov-2,covid-19 vaccine

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