title: Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors.
abstract: Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction. A close relative of gammaretroviruses, HERV-T, circulated in primates for ~25 million years (MY) before apparent extinction within the past ~8 MY. Construction of a near-complete catalog of HERV-T fossils in primate genomes allowed us to estimate a ~32 MY old ancestral sequence and reconstruct a functional envelope protein (ancHTenv) that could support infection of a pseudotyped modern gammaretrovirus. Using ancHTenv, we identify monocarboxylate transporter-1 (MCT-1) as a receptor used by HERV-T for attachment and infection. A single HERV-T provirus in hominid genomes includes anenvgene (hsaHTenv) that has been uniquely preserved. This apparently exapted HERV-Tenvcould not support virion infection but could block ancHTenv mediated infection, by causing MCT-1 depletion from cell surfaces. Thus, hsaHTenv may have contributed to HERV-T extinction, and could also potentially regulate cellular metabolism.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, United States.|Laboratory of Retrovirology, The Rockefeller University, New York, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Blanco-Melo
authors.affiliation: MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
authors.forename: Robert J
authors.identifier: 0000-0003-4028-9884
authors.initials: RJ
authors.lastname: Gifford
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, United States.|Laboratory of Retrovirology, The Rockefeller University, New York, United States.|Howard Hughes Medical Institute, The Rockefeller University, New York, United States.
authors.forename: Paul D
authors.identifier: 0000-0002-2368-3719
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000818:Animals; D020077:Endogenous Retroviruses / Q000235:genetics*; D017988:Gammaretrovirus / Q000235:genetics / Q000254:growth & development; D015686:Gene Products, env / Q000235:genetics*; D015186:Hominidae / Q000235:genetics* / Q000821:virology; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D053585:Virus Attachment; D053586:Virus Internalization; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D015686:Gene Products, env; D027501:Monocarboxylic Acid Transporters; D011991:Receptors, Virus; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1
keywords: Endogenous retrovirus; Hominid; Paleovirology; evolutionary biology; genomics; human; infectious disease; microbiology; receptors; virus