Retroviral DNA integration: viral and cellular determinants of target-site selection.

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Version: author
Serval ID
serval:BIB_EDB114A2B2E1
Type
Article: article from journal or magazin.
Collection
Publications
Title
Retroviral DNA integration: viral and cellular determinants of target-site selection.
Journal
PLoS Pathogens
Author(s)
Lewinski M.K., Yamashita M., Emerman M., Ciuffi A., Marshall H., Crawford G., Collins F., Shinn P., Leipzig J., Hannenhalli S., Berry C.C., Ecker J.R., Bushman F.D.
ISSN
1553-7374
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
2
Number
6
Pages
e60
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't - old month value : Jun
Abstract
Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN) coding region into HIV (to make HIVmIN) caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN) further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag) displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb), and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.
Keywords
Attachment Sites, Microbiological, Binding Sites, Chimera, Cloning, Molecular, CpG Islands, DNA, Viral, Deoxyribonuclease I, Gene Transfer Techniques, Glycosaminoglycans, HIV, Hela Cells, Humans, Integrases, Leukemia Virus, Murine, Puromycin, Retroviridae, Transcription Factors, Transcription Initiation Site, Transduction, Genetic, Virus Integration
Pubmed
Web of science
Open Access
Yes
Create date
22/02/2008 15:45
Last modification date
20/08/2019 17:15
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