LINE-1 retrotransposons facilitate horizontal gene transfer into poxviruses
Abstract
There is ample phylogenetic evidence that many critical virus functions, like immune evasion, evolved by the acquisition of genes from their hosts through horizontal gene transfer (HGT). However, the lack of an experimental system has prevented a mechanistic understanding of this process. We developed a model to elucidate the mechanisms of HGT into vaccinia virus, the prototypic poxvirus. All identified gene capture events showed signatures of long interspersed nuclear element-1 (LINE-1)-mediated retrotransposition, including spliced-out introns, polyadenylated tails, and target site duplications. In one case, the acquired gene integrated together with a polyadenylated host U2 small nuclear RNA. Integrations occurred across the genome, in some cases knocking out essential viral genes. These essential gene knockouts were rescued through a process of complementation by the parent virus followed by non-homologous recombination during serial passaging to generate a single, replication-competent virus. This work links multiple evolutionary mechanisms into one adaptive cascade and identifies host retrotransposons as major drivers for virus evolution.
Data availability
Sequencing data have been deposited in ArrayExpress under accession code E-MTAB-9682.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI146915)
- Stefan Rothenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Karla Kirkegaard, Stanford University School of Medicine, United States
Version history
- Received: September 22, 2020
- Preprint posted: October 26, 2020 (view preprint)
- Accepted: September 6, 2022
- Accepted Manuscript published: September 7, 2022 (version 1)
- Version of Record published: October 18, 2022 (version 2)
Copyright
© 2022, Rahman 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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Further reading
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- Evolutionary Biology
- Microbiology and Infectious Disease
As long suspected, poxviruses capture host genes through a reverse-transcription process now shown to be mediated by retrotransposons.
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