Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses

We demonstrated previously that the cytosine deaminase APOBEC3G inhibits retrotransposition of two active murine endogenous retroviruses, namely intracisternal A-particles (IAP) and MusD, in an ex vivo assay where retrotransposition was monitored by selection of neo-marked elements. Sequencing of th...

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Main Authors:	Esnault, Cécile, Millet, Jean, Schwartz, Olivier, Heidmann, Thierry
Format:	Online
Language:	English
Published:	Oxford University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401513/

id	pubmed-1401513
recordtype	oai_dc
spelling	pubmed-14015132006-03-16 Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses Esnault, Cécile Millet, Jean Schwartz, Olivier Heidmann, Thierry Article We demonstrated previously that the cytosine deaminase APOBEC3G inhibits retrotransposition of two active murine endogenous retroviruses, namely intracisternal A-particles (IAP) and MusD, in an ex vivo assay where retrotransposition was monitored by selection of neo-marked elements. Sequencing of the transposed copies further disclosed extensive editing, resulting in a high load of G-to-A mutations. Here, we asked whether this G-to-A editing was associated with an impact of APOBEC3G on viral cDNA yields. To this end, we used a specially designed quantitative PCR method to selectively measure the copy number of transposed retroelements, in the absence of G418 selection. We show that human APOBEC3G severely reduces the number of MusD and IAP transposed cDNA copies, with no effect on the level of the intermediate RNA transcripts. The magnitude of the decrease closely parallels that observed when transposed copies are assayed by selection of G418-resistant cells. Moreover, sequencing of transposed elements recovered by PCR without prior selection of the cells reveals high-level editing. Using this direct method with a series of cytosine deaminases, we further demonstrate a similar dual effect of African green monkey APOBE3G, human APOBEC3F and murine APOBEC3 on MusD retrotransposition, with a distinct extent and site specificity for each editing activity. Altogether the data demonstrate that cytosine deaminases have a protective effect against endogenous retroviruses both by reducing viral cDNA levels and by introducing mutations in the transposed copies, thus inactivating them for subsequent rounds of retrotransposition. This dual, two-step effect likely participates in the efficient defense of the cell genome against invading endogenous retroelements. Oxford University Press 2006 2006-03-14 /pmc/articles/PMC1401513/ /pubmed/16537839 http://dx.doi.org/10.1093/nar/gkl054 Text en © The Author 2006. Published by Oxford University Press. All rights reserved
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Esnault, Cécile Millet, Jean Schwartz, Olivier Heidmann, Thierry
spellingShingle	Esnault, Cécile Millet, Jean Schwartz, Olivier Heidmann, Thierry Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
author_facet	Esnault, Cécile Millet, Jean Schwartz, Olivier Heidmann, Thierry
author_sort	Esnault, Cécile
title	Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
title_short	Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
title_full	Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
title_fullStr	Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
title_full_unstemmed	Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses
title_sort	dual inhibitory effects of apobec family proteins on retrotransposition of mammalian endogenous retroviruses
description	We demonstrated previously that the cytosine deaminase APOBEC3G inhibits retrotransposition of two active murine endogenous retroviruses, namely intracisternal A-particles (IAP) and MusD, in an ex vivo assay where retrotransposition was monitored by selection of neo-marked elements. Sequencing of the transposed copies further disclosed extensive editing, resulting in a high load of G-to-A mutations. Here, we asked whether this G-to-A editing was associated with an impact of APOBEC3G on viral cDNA yields. To this end, we used a specially designed quantitative PCR method to selectively measure the copy number of transposed retroelements, in the absence of G418 selection. We show that human APOBEC3G severely reduces the number of MusD and IAP transposed cDNA copies, with no effect on the level of the intermediate RNA transcripts. The magnitude of the decrease closely parallels that observed when transposed copies are assayed by selection of G418-resistant cells. Moreover, sequencing of transposed elements recovered by PCR without prior selection of the cells reveals high-level editing. Using this direct method with a series of cytosine deaminases, we further demonstrate a similar dual effect of African green monkey APOBE3G, human APOBEC3F and murine APOBEC3 on MusD retrotransposition, with a distinct extent and site specificity for each editing activity. Altogether the data demonstrate that cytosine deaminases have a protective effect against endogenous retroviruses both by reducing viral cDNA levels and by introducing mutations in the transposed copies, thus inactivating them for subsequent rounds of retrotransposition. This dual, two-step effect likely participates in the efficient defense of the cell genome against invading endogenous retroelements.
publisher	Oxford University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1401513/
_version_	1611381220778704896

Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses

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