Recombinant origin and interspecies transmission of a HERV-K(HML-2)-related primate retrovirus with a novel RNA transport element
- Boston College, United States
- Tufts University, United States
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.
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Generation of Naïve Induced Pluripotent Stem Cells from Rhesus Monkey FibroblastsNCBI Sequence Read Archive, SRR1575130.
Article and author information
Author details
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.
Reviewing Editor
- Detlef Weigel, Max Planck Institute for Biology Tübingen, Germany
Version history
- Received: May 24, 2022
- Accepted: July 20, 2024
- Accepted Manuscript published: July 22, 2024 (version 1)
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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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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