HIV integration site selection: targeting in macrophages and the effects of different routes of viral entry.
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.
Barr
Stephen D
SD
Department of Microbiology, University of Pennsylvania School of Medicine, 3610 Hamilton Walk, Philadelphia, 19104-6076, USA.
Ciuffi
Angela
A
Leipzig
Jeremy
J
Shinn
Paul
P
Ecker
Joseph R
JR
Bushman
Frederic D
FD
D001483:Base Sequence; D019295:Computational Biology; D015894:Genome, Human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008562:Membrane Glycoproteins / Q000502:physiology; D015728:Receptors, HIV / Q000502:physiology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000821:virology; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000502:physiology; D016662:Virus Integration / Q000502:physiology*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D015728:Receptors, HIV; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor