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Cited by 14Chromosomal and Genetic VariationsRNA Research and SplicingGenomics and Chromatin Dynamics

Intercellular viral spread and intracellular transposition of Drosophila gypsy

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Keegan, Richard M., Talbot, Lillian R., Chang, Yung-Heng, Metzger, Michael J., Dubnau, Josh·2021·PLOS Genetics
DOI 10.1371/journal.pgen.1009535PMC PMC8096092

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Abstract

It has become increasingly clear that retrotransposons (RTEs) are more widely expressed in somatic tissues than previously appreciated. RTE expression has been implicated in a myriad of biological processes ranging from normal development and aging, to age related diseases such as cancer and neurodegeneration. Long Terminal Repeat (LTR)-RTEs are evolutionary ancestors to, and share many features with, exogenous retroviruses. In fact, many organisms contain endogenous retroviruses (ERVs) derived from exogenous retroviruses that integrated into the germ line. These ERVs are inherited in Mendelian fashion like RTEs, and some retain the ability to transmit between cells like viruses, while others develop the ability to act as RTEs. The process of evolutionary transition between LTR-RTE and retroviruses is thought to involve multiple steps by which the element loses or gains the ability to transmit copies between cells versus the ability to replicate intracellularly. But, typically, these two modes of transmission are incompatible because they require assembly in different sub-cellular compartments. Like murine IAP/IAP-E elements, the gypsy family of retroelements in arthropods appear to sit along this evolutionary transition. Indeed, there is some evidence that gypsy may exhibit retroviral properties. Given that gypsy elements have been found to actively mobilize in neurons and glial cells during normal aging and in models of neurodegeneration, this raises the question of whether gypsy replication in somatic cells occurs via intracellular retrotransposition, intercellular viral spread, or some combination of the two. These modes of replication in somatic tissues would have quite different biological implications. Here, we demonstrate that Drosophila gypsy is capable of both cell-associated and cell-free viral transmission between cultured S2 cells of somatic origin. Further, we demonstrate that the ability of gypsy to move between cells is dependent upon a functional copy of its viral envelope protein. This argues that the gypsy element has transitioned from an RTE into a functional endogenous retrovirus with the acquisition of its envelope gene. On the other hand, we also find that intracellular retrotransposition of the same genomic copy of gypsy can occur in the absence of the Env protein. Thus, gypsy exhibits both intracellular retrotransposition and intercellular viral transmission as modes of replicating its genome.

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  • The Drosophila genome harbors fully functional copies of mdg4, and there is direct evidence for intercellular viral transmission that requires the Env gene.

    “The Drosophila genome harbors fully functional copies of mdg4, and there is direct evidence for intercellular viral transmission that requires the Env gene”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Keegan et al. 2021

    The Results (‘Intercellular transmission of gypsy requires Env’; page unavailable) directly show cell-free transmission of gypsy in cultured S2 cells and that deleting Env nearly abolishes it. The Discussion says intact gypsy copies in the Drosophila reference genome appear to contain an Env reading frame, but our copy does not identify them as mdg4 or establish that those genomic copies are fully functional. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Drosophila mdg4 contains a functional Env gene that enables both cell-associated and cell-free viral transmission between cultured S2 cells.

    “Similar to HERV-K (Contreras-Galindo et al. 2015, Dewannieux et al. 2006, Lee & Bieniasz 2007), Drosophila mdg4 contains a functional Env gene that enables both cell-associated and cell-free viral transmission between cultured S2 cells (Keegan et al. 2021).”

    From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Keegan et al. 2021

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Cited by

Sorted by citations

Authors
Keegan, R. M., Talbot, L. R., Chang, Y.-H., Metzger, M. J., & Dubnau, J.
Affiliations
  • Stony Brook University (US)
  • Stony Brook School (US)
Corresponding author
Dubnau, Josh
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2021-04-22
Volume
17
Issue
4
Pages
e1009535
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1009535
PMC
PMC8096092
OpenAlex
W3155206464
Cited by
14
References
17
Citations by year
2026: 1 · 2024: 3 · 2023: 3 · 2022: 7
FWCI
1.95
Type
journal article
Language
en
Update notices
new_version (2021-05-04)
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Neurological Disorders and Stroke (5R01NS091748)
  • National Institute on Aging (1RF1AG057338)
  • National Institutes of Health (K22 CA226047)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
retrotransposons, endogenous retroviruses, viral envelope proteins, retroviral evolution, S2 cells
MeSH terms
Animals, Drosophila melanogaster, Humans, Neoplasms, Nerve Degeneration, Neurons, Retroelements, Evolution, Molecular, Endogenous Retroviruses, Terminal Repeat Sequences, Mice

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