Syncytin 1 dependent horizontal transfer of marker genes from retrovirally transduced cells.
Autor: | Uygur B; Section on Membrane Biology, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Melikov K; Section on Membrane Biology, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Arakelyan A; Section of Intercellular Interactions, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Margolis LB; Section of Intercellular Interactions, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA., Chernomordik LV; Section on Membrane Biology, Eunice Kennedy National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. chernoml@mail.nih.gov. |
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Jazyk: | angličtina |
Zdroj: | Scientific reports [Sci Rep] 2019 Nov 27; Vol. 9 (1), pp. 17637. Date of Electronic Publication: 2019 Nov 27. |
DOI: | 10.1038/s41598-019-54178-y |
Abstrakt: | Retroviral transduction is routinely used to generate cell lines expressing exogenous non-viral genes. Here, we show that human cells transduced to stably express GFP transfer GFP gene to non-transduced cells. This horizontal gene transfer was mediated by a fraction of extracellular membrane vesicles that were released by the transduced cells. These vesicles carried endogenous retroviral envelope protein syncytin 1 and essentially acted as replication-competent retroviruses. The ability to transfer the GFP gene correlated with the levels of syncytin 1 expression in the transduced cells and depended on the fusogenic activity of this protein, substantiating the hypothesis that endogenous syncytin 1 mediates fusion stage in the delivery of extracellular vesicle cargo into target cells. Our findings suggest that testing for replication-competent retroviruses, a routine safety test for transduced cell products in clinical studies, should be also carried out for cell lines generated by retroviral vectors in in vitro studies. |
Databáze: | MEDLINE |
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