1. ¹Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104-6076, USA
2. ²Department of Medical Microbiology and Immunology, University of Alberta, 632 Heritage Medical Research Center, Edmonton, AB, Canada T6G 2S2
3. ³Genomic Analysis Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA

Correspondence: Frederic D. Bushman, E-mail: bushman@mail.med.upenn.edu

Received 4 January 2006; Revised 14 February 2006; Accepted 5 March 2006.

Abstract

We have studied the selection of HIV DNA integration sites in primary macrophages to investigate two questions. First, mature macrophages do not divide, allowing us to investigate whether HIV integration targeting differs between dividing cells and nondividing cells. We sequenced and analyzed 754 unique integration sites and found that integration in macrophages is favored in active transcription units (TUs), as was observed previously for other cell types. However, HIV integration in genes was slightly less favored in macrophages than in dividing PBMC or T cell lines. Second, we compared integration targeting by HIV-vector particles bearing either of two different envelope proteins (HIV R5 Env or VSV-G) to determine whether the mechanism of entry influenced subsequent integration targeting. Integration sites generated by HIV R5- or VSV-G-bearing particles showed no significant differences in their distributions in the human genome. Analysis of additional published integration site sequences also indicated that the route of entry did not affect integration site selection for other viral envelopes as well.