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

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

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Aaron Diamond AIDS Research Center, The Rockefeller University, New York, United States.
Laboratory of Retrovirology, The Rockefeller University, New York, United States.
MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom.
Howard Hughes Medical Institute, The Rockefeller University, New York, United States.


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.


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

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