Evolution and antiviral activity of a human protein of retroviral origin

Author:

Frank John A.1ORCID,Singh Manvendra1,Cullen Harrison B.1ORCID,Kirou Raphael A.1ORCID,Benkaddour-Boumzaouad Meriem2,Cortes Jose L.23,Garcia Pérez Jose24ORCID,Coyne Carolyn B.5ORCID,Feschotte Cédric1ORCID

Affiliation:

1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.

2. GENYO Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Spain.

3. Eppendorf, Iberica, Spain.

4. MRC-Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.

5. Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC, USA.

Abstract

Endogenous retroviruses are abundant components of mammalian genomes descended from ancient germline infections. In several mammals, the envelope proteins encoded by these elements protect against exogenous viruses, but this activity has not been documented with endogenously expressed envelopes in humans. We report that the human genome harbors a large pool of envelope-derived sequences with the potential to restrict retroviral infection. To test this, we characterized an envelope-derived protein, Suppressyn. We found that Suppressyn is expressed in human preimplantation embryos and developing placenta using its ancestral retroviral promoter. Cell culture assays showed that Suppressyn , and its hominoid orthologs, could restrict infection by extant mammalian type D retroviruses. Our data support a generalizable model of retroviral envelope co-option for host immunity and genome defense.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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