Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors

Elife. 2017 Apr 11;6:e22519. doi: 10.7554/eLife.22519.


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 an env gene (hsaHTenv) that has been uniquely preserved. This apparently exapted HERV-T env could 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.

Keywords: Endogenous retrovirus; Hominid; Paleovirology; evolutionary biology; genomics; human; infectious disease; microbiology; receptors; virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endogenous Retroviruses / genetics*
  • Gammaretrovirus / genetics
  • Gammaretrovirus / growth & development
  • Gene Products, env / genetics*
  • Hominidae / genetics*
  • Hominidae / virology
  • Monocarboxylic Acid Transporters / metabolism
  • Receptors, Virus / metabolism
  • Symporters / metabolism
  • Virus Attachment
  • Virus Internalization


  • Gene Products, env
  • Monocarboxylic Acid Transporters
  • Receptors, Virus
  • Symporters
  • monocarboxylate transport protein 1