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

Publication ,  Journal Article
Lewinski, MK; Yamashita, M; Emerman, M; Ciuffi, A; Marshall, H; Crawford, G; Collins, F; Shinn, P; Leipzig, J; Hannenhalli, S; Berry, CC ...
Published in: PLoS Pathog
June 2006

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.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

June 2006

Volume

2

Issue

6

Start / End Page

e60

Location

United States

Related Subject Headings

  • Virus Integration
  • Virology
  • Transduction, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Retroviridae
  • Puromycin
  • Leukemia Virus, Murine
  • Integrases
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lewinski, M. K., Yamashita, M., Emerman, M., Ciuffi, A., Marshall, H., Crawford, G., … Bushman, F. D. (2006). Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog, 2(6), e60. https://doi.org/10.1371/journal.ppat.0020060
Lewinski, Mary K., Masahiro Yamashita, Michael Emerman, Angela Ciuffi, Heather Marshall, Gregory Crawford, Francis Collins, et al. “Retroviral DNA integration: viral and cellular determinants of target-site selection.PLoS Pathog 2, no. 6 (June 2006): e60. https://doi.org/10.1371/journal.ppat.0020060.
Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, Crawford G, et al. Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog. 2006 Jun;2(6):e60.
Lewinski, Mary K., et al. “Retroviral DNA integration: viral and cellular determinants of target-site selection.PLoS Pathog, vol. 2, no. 6, June 2006, p. e60. Pubmed, doi:10.1371/journal.ppat.0020060.
Lewinski MK, Yamashita M, Emerman M, Ciuffi A, Marshall H, Crawford G, Collins F, Shinn P, Leipzig J, Hannenhalli S, Berry CC, Ecker JR, Bushman FD. Retroviral DNA integration: viral and cellular determinants of target-site selection. PLoS Pathog. 2006 Jun;2(6):e60.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

June 2006

Volume

2

Issue

6

Start / End Page

e60

Location

United States

Related Subject Headings

  • Virus Integration
  • Virology
  • Transduction, Genetic
  • Transcription Initiation Site
  • Transcription Factors
  • Retroviridae
  • Puromycin
  • Leukemia Virus, Murine
  • Integrases
  • Humans