Recombinant origin and interspecies transmission of a HERV-K(HML-2)-related primate retrovirus with a novel RNA transport element

Abstract

HERV-K(HML-2), the youngest clade of human endogenous retroviruses (HERVs), includes many intact or nearly intact proviruses, but no replication competent HML-2 proviruses have been identified in humans. HML-2-related proviruses are present in other primates, including rhesus macaques, but the extent and timing of HML-2 activity in macaques remains unclear. We have identified 145 HML-2-like proviruses in rhesus macaques, including a clade of young, rhesus-specific insertions. Age estimates, intact ORFs, and insertional polymorphism of these insertions are consistent with recent or ongoing infectious activity in macaques. 106 of the proviruses form a clade characterized by an ~750 bp sequence between env and the 3' LTR, derived from an ancient recombination with a HERV-K(HML-8)-related virus. This clade is found in Old World monkeys (OWM), but not great apes, suggesting it originated after the ape/OWM split. We identified similar proviruses in white-cheeked gibbons; the gibbon insertions cluster within the OWM recombinant clade, suggesting interspecies transmission from OWM to gibbons. The LTRs of the youngest proviruses have deletions in U3, which disrupt the Rec Response Element (RcRE), required for nuclear export of unspliced viral RNA. We show that the HML-8 derived region functions as a Rec-independent constitutive transport element (CTE), indicating the ancestral Rec-RcRE export system was replaced by a CTE mechanism.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files, or are re-analyses of publically available data; source data files have been provided for Figures 1-5 and 7-8.

The following previously published data sets were used

Article and author information

Author details

  1. Zachary H Williams

    Department of Biology, Boston College, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Alvaro Dafonte Imedio

    Department of Biology, Boston College, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lea Gaucherand

    Molecular Microbiology Program, Tufts University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4477-1021
  4. Derek C Lee

    Department of Biology, Boston College, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Salwa Mohd Mostafa

    Department of Developmental, Molecular and Chemical Biology, Tufts University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. James P Phelan

    Molecular Microbiology Program, Tufts University, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. John M Coffin

    Department of Molecular Biology and Microbiology, Tufts University, Medford, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Welkin E Johnson

    Department of Biology, Boston College, Chestnut Hill, United States
    For correspondence
    welkin.johnson@bc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5991-5414

Funding

National Institute of Allergy and Infectious Diseases (AI083118)

  • Zachary H Williams
  • Alvaro Dafonte Imedio
  • Derek C Lee

National Institute of Allergy and Infectious Diseases (AI136074)

  • Zachary H Williams
  • Alvaro Dafonte Imedio
  • Derek C Lee

National Cancer Institute (R35CA200421)

  • Zachary H Williams
  • Lea Gaucherand
  • Salwa Mohd Mostafa
  • James P Phelan
  • John M Coffin

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2024, Williams et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zachary H Williams
  2. Alvaro Dafonte Imedio
  3. Lea Gaucherand
  4. Derek C Lee
  5. Salwa Mohd Mostafa
  6. James P Phelan
  7. John M Coffin
  8. Welkin E Johnson
(2024)
Recombinant origin and interspecies transmission of a HERV-K(HML-2)-related primate retrovirus with a novel RNA transport element
eLife 13:e80216.
https://doi.org/10.7554/eLife.80216

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https://doi.org/10.7554/eLife.80216