Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses
13 pages
English
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Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses

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13 pages
English

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The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of host-pathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and non-LTR endogenous retroelements. Most significantly, RNAi-mediated silencing of endogenous MOV10 enhanced the replication of both LTR and non-LTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNA-mediated mRNA silencing. Conclusions We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells.

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Publié le 01 janvier 2012
Nombre de lectures 12
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ArjanOdedraet al. Retrovirology2012,9:53 http://www.retrovirology.com/content/9/1/53
R E S E A R C HOpen Access Endogenous MOV10 inhibits the retrotransposition of endogenous retroelements but not the replication of exogenous retroviruses 1 11,3 21* Shetal ArjanOdedra , Chad M Swanson , Nathan M Sherer, Steven M Wolinskyand Michael H Malim
Abstract Background:The identification of cellular factors that regulate the replication of exogenous viruses and endogenous mobile elements provides fundamental understanding of hostpathogen relationships. MOV10 is a superfamily 1 putative RNA helicase that controls the replication of several RNA viruses and whose homologs are necessary for the repression of endogenous mobile elements. Here, we employ both ectopic expression and gene knockdown approaches to analyse the role of human MOV10 in the replication of a panel of exogenous retroviruses and endogenous retroelements. Results:MOV10 overexpression substantially decreased the production of infectious retrovirus particles, as well the propagation of LTR and nonLTR endogenous retroelements. Most significantly, RNAimediated silencing of endogenous MOV10 enhanced the replication of both LTR and nonLTR endogenous retroelements, but not the production of infectious retrovirus particles demonstrating that natural levels of MOV10 suppress retrotransposition, but have no impact on infection by exogenous retroviruses. Furthermore, functional studies showed that MOV10 is not necessary for miRNA or siRNAmediated mRNA silencing. Conclusions:We have identified novel specificity for human MOV10 in the control of retroelement replication and hypothesise that MOV10 may be a component of a cellular pathway or process that selectively regulates the replication of endogenous retroelements in somatic cells. Keywords:MOV10, Retrovirus, Retrotransposon, APOBEC3
Background Exogenous retroviruses and endogenous retroelements replicate in the host by reverse transcribing their RNA genomes into DNA copies that are permanently integrated into the host genome, making them some of the most suc cessful parasites studied. Approximately 45% of the human genome is derived from mobile elements, with ac tive long interspersed nucleotide element1 (LINE1), Alu and SINER/VNTR/Alu (SVA) retrotransposition events contributing to diseaseproducing insertional mutations in humans [14]. Host cells have evolved multiple tran scriptional and posttranscriptional control mechanisms
* Correspondence: michael.malim@kcl.ac.uk 1 Department of Infectious Diseases, King's College London School of Medicine, 2nd Floor, Borough Wing, Guy's Hospital, London Bridge, London, SE1 9RT, UK Full list of author information is available at the end of the article
to protect themselves and their genomes from the pathogenic and mutagenic effects of such parasites. Cellular restriction factors form an effective innate defence against a range of exogenous retroviruses and intracellular retroelements. The human APOBEC3 (apo lipoprotein B mRNAediting enzymecatalytic polypep tide 1like 3) family of cytidine deaminases are potent intrinsic antiviral factors that restrict a broad range of exogenous retroviruses [59] as well as the propagation of numerous endogenous retroelements [610]. Similarly, TRIM5α[11], tetherin [12] and SAMHD1 [13,14] are restriction factors that can inhibit the replication of ex ogenous retroviruses at different steps in the retroviral life cycle [15]. Intriguingly, the cytosolic exonuclease TREX1 metabolises reversetranscribed DNA derived from endogenous retroelements and, presumably, restricts their retrotransposition [16], yet is a cofactor for human immunodeficiency virus type1 (HIV1)
© 2012 ArjanOdedra et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.