Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues

ABSTRACT EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative rec...

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Autores principales:	Kevin R. McCarthy, Joseph L. Timpona, Simon Jenni, Louis-Marie Bloyet, Vesna Brusic, Welkin E. Johnson, Sean P. J. Whelan, Lindsey R. Robinson-McCarthy
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	endogenous retrovirus envelope protein paleovirology structure evolution Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/98868e82129a490397d8d207d2023a7b
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spelling	oai:doaj.org-article:98868e82129a490397d8d207d2023a7b2021-11-15T15:55:43ZStructure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues10.1128/mBio.02772-202150-7511https://doaj.org/article/98868e82129a490397d8d207d2023a7b2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02772-20https://doaj.org/toc/2150-7511ABSTRACT EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying selection and its fusogenic activity has been maintained for over 40 million years. We determined the structure of the RBD of human EnvP(b)1, which defines structural similarities with extant leukemia viruses, despite little sequence conservation. This structure highlights a common scaffold from which novel receptor binding specificities likely evolved. The evolutionary plasticity of this domain may underlie the diversity of related Envs in circulating viruses. IMPORTANCE Organisms can access genetic and functional novelty by capturing viral elements within their genomes, where they can evolve to drive new cellular or organismal processes. We demonstrate that a retroviral envelope gene, EnvP(b)1, has been maintained and its fusion activity preserved for 40 to 71 million years. It is expressed as a protein in multiple healthy human tissues. We determined the structure of its inferred receptor binding domain and compared it with the same domain in modern viruses. We found a common conserved architecture that underlies the varied receptor binding activity of divergent Env genes. The modularity and versatility of this domain may underpin the evolutionary success of this clade of fusogens.Kevin R. McCarthyJoseph L. TimponaSimon JenniLouis-Marie BloyetVesna BrusicWelkin E. JohnsonSean P. J. WhelanLindsey R. Robinson-McCarthyAmerican Society for Microbiologyarticleendogenous retrovirusenvelope proteinpaleovirologystructureevolutionMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	endogenous retrovirus envelope protein paleovirology structure evolution Microbiology QR1-502
spellingShingle	endogenous retrovirus envelope protein paleovirology structure evolution Microbiology QR1-502 Kevin R. McCarthy Joseph L. Timpona Simon Jenni Louis-Marie Bloyet Vesna Brusic Welkin E. Johnson Sean P. J. Whelan Lindsey R. Robinson-McCarthy Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
description	ABSTRACT EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying selection and its fusogenic activity has been maintained for over 40 million years. We determined the structure of the RBD of human EnvP(b)1, which defines structural similarities with extant leukemia viruses, despite little sequence conservation. This structure highlights a common scaffold from which novel receptor binding specificities likely evolved. The evolutionary plasticity of this domain may underlie the diversity of related Envs in circulating viruses. IMPORTANCE Organisms can access genetic and functional novelty by capturing viral elements within their genomes, where they can evolve to drive new cellular or organismal processes. We demonstrate that a retroviral envelope gene, EnvP(b)1, has been maintained and its fusion activity preserved for 40 to 71 million years. It is expressed as a protein in multiple healthy human tissues. We determined the structure of its inferred receptor binding domain and compared it with the same domain in modern viruses. We found a common conserved architecture that underlies the varied receptor binding activity of divergent Env genes. The modularity and versatility of this domain may underpin the evolutionary success of this clade of fusogens.
format	article
author	Kevin R. McCarthy Joseph L. Timpona Simon Jenni Louis-Marie Bloyet Vesna Brusic Welkin E. Johnson Sean P. J. Whelan Lindsey R. Robinson-McCarthy
author_facet	Kevin R. McCarthy Joseph L. Timpona Simon Jenni Louis-Marie Bloyet Vesna Brusic Welkin E. Johnson Sean P. J. Whelan Lindsey R. Robinson-McCarthy
author_sort	Kevin R. McCarthy
title	Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
title_short	Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
title_full	Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
title_fullStr	Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
title_full_unstemmed	Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues
title_sort	structure of the receptor binding domain of envp(b)1, an endogenous retroviral envelope protein expressed in human tissues
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/98868e82129a490397d8d207d2023a7b
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Structure of the Receptor Binding Domain of EnvP(b)1, an Endogenous Retroviral Envelope Protein Expressed in Human Tissues

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