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Journal of Virology, February 2009, p. 1920-1929, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.00856-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genome Areas with High Gene Density and CpG Island Neighborhood Strongly Attract Porcine Endogenous Retrovirus for Integration and Favor the Formation of Hot Spots{triangledown} ,{dagger}

Y. Moalic,1 H. Félix,1 Y. Takeuchi,2 A. Jestin,1 and Y. Blanchard1*

Unité de Génétique Virale et Biosécurité, AFSSA-LERAPP, BP 53, 22440 Ploufragan, France,1 Wohl Virion Centre, Division of Infection and Immunity, University College London, London W1T 4JF, United Kingdom2

Received 23 April 2008/ Accepted 18 November 2008

Porcine endogenous retroviruses (PERV) are members of the gammaretrovirus genus and display integration preferences around transcription start sites, a finding which is similar to the preferences of the murine leukemia virus (MLV). Our new genome-wide analysis of the integration profile of a recombinant PERV (PERV A/C), enabled us to examine more than 1,900 integration sites and identify 224 integration hot spots. Investigation of the possible genome features involved in hot-spot formation revealed that the expression level of the genes did not influence distribution of the integration sites of gammaretroviruses (PERV and MLV) or the formation of integration hot spots. However, PERV integration and the presence of hot spots was found to be greater in areas of the genome with high densities of genes with CpG islands. Surprisingly, this was not true for MLV. Simulation of integration profiles revealed that retrovirus integration studies involving the use of the restriction enzyme MseI (widely used in genome integration studies of MLV and gammaretroviral vector) underestimated integration near CpG islands and in gene-dense areas. These results suggest that the integration of gammaretrovirus or gammaretroviral vectors might occur preferentially in genome areas that are highly enriched in genes under CpG island promoter regulation.

* Corresponding author. Mailing address: Unité de Génétique Virale et Biosécurité, AFSSA-LERAPP, BP 53, 22440 Ploufragan, France. Phone: 33 2 96 01 62 97. Fax: 33 2 96 01 62 83. E-mail: y.blanchard{at}afssa.fr

{triangledown} Published ahead of print on 26 November 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, February 2009, p. 1920-1929, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.00856-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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