JVI Accepts, published online ahead of print on 26 November 2008

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J. Virol. doi:10.1128/JVI.00856-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Genome areas with high gene density and CpG island neighbourhood strongly attract PERV for integration and favour hot spots formation

Y Moalic, H Félix, Y Takeuchi, A Jestin, and Y Blanchard^*

Unité de Génétique Viral et Biosécurité, AFSSA –LERAPP, BP 53, 22440 PLOUFRAGAN, FRANCE; Wohl Virion Centre, Division of Infection and Immunity, University College London, W1T 4JF, London, United Kingdom

^* To whom correspondence should be addressed. Email: y.blanchard{at}afssa.fr.

Porcine endogenous retroviruses (PERV) are members of the gammaretrovirus genus and display integration preferences around transcription start sites, similar to those 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 1900 integration sites and identify 224 integration hot spots. Investigation of the possible genome features involved in hot spots 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 gene with CpG islands. Surprisingly this was not found true for MLV. Simulation of integration profiles revealed that retrovirus integration studies involving the use of 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.