Intercellular viral spread and intracellular transposition of Drosophila gypsy
Autoři:
Richard M. Keegan aff001; Lillian R. Talbot aff002; Yung-Heng Chang aff003; Michael J. Metzger aff004; Josh Dubnau aff001
Působiště autorů:
Program in Neuroscience, Department of Neurobiology and Behavior, Stony Brook University, New York City, New York, United States of America
aff001; Medical Scientist Training Program, Department of Neurobiology and Behavior, Stony Brook University, New York City, New York, United States of America
aff002; Department of Anesthesiology, Stony Brook School of Medicine, New York City, New York, United States of America
aff003; Pacific Northwest Research Institute, Seattle, Washington, United States of America
aff004
Vyšlo v časopise:
Intercellular viral spread and intracellular transposition of Drosophila gypsy. PLoS Genet 17(4): e1009535. doi:10.1371/journal.pgen.1009535
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009535
Souhrn
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.
Klíčová slova:
Drosophila melanogaster – Fluorescence imaging – Invertebrate genomics – Polymerase chain reaction – Retroviruses – Romani people – Transfection – Viral replication
Zdroje
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