Poxviruses capture host genes by LINE-1 retrotransposition
Abstract
Horizontal gene transfer (HGT) provides a major source of genetic variation. Many viruses, including poxviruses, encode genes with crucial functions directly gained by gene transfer from hosts. The mechanism of transfer to poxvirus genomes is unknown. Using genome analysis and experimental screens of infected cells, we discovered a central role for Long Interspersed Nuclear Element-1 (LINE-1) retrotransposition in HGT to virus genomes. The process recapitulates processed pseudogene generation, but with host messenger RNA directed into virus genomes. Intriguingly, hallmark features of retrotransposition appear to favor virus adaption through rapid duplication of captured host genes on arrival. Our study reveals a previously unrecognized conduit of genetic traffic with fundamental implications for the evolution of many virus classes and their hosts.
Data availability
Sequencing data have been deposited in the NCBI SRA database under project code PRJNA614958.All data generated or analyses during this study are included in the manuscript and supplemental files.
Article and author information
Author details
Funding
National Institutes of Health (R35GM134936)
- Nels C Elde
National Institutes of Health (T32GM007464)
- Sarah M Fixsen
- Thomas A Sasani
National Institutes of Health (T32AI055434)
- Kelsey R Cone
Burroughs Wellcome Fund (1015462)
- Nels C Elde
University of Utah (HA and Edna Benning Presidential Endowed Chair)
- Nels C Elde
National Institutes of Health (R01AI146915)
- Stefan Rothenburg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Fixsen 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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- Chromosomes and Gene Expression
- Evolutionary Biology
Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.