Astrid R.W. Schröder 1, Paul Shinn 2, Huaming Chen 2, Charles Berry 3, Joseph R. Ecker 2, and Frederic Bushman 1
1 Infectious Disease Laboratory, The Salk Institute, 10010
North Torrey Pines Road, La Jolla, CA 92037 USA
2 Genomic Analysis Laboratory, The Salk Institute, 10010
North Torrey Pines Road, La Jolla, CA 92037 USA
3 Department of Family/Preventive Medicine, School of
Medicine, University of California, San Diego, San Diego, CA 92093 USA
Correspondence: Frederic Bushman 858-453-4100 ext.
1630 (phone), 858-554-0341 (fax)
bushman@salk.edu
A defining feature of HIV replication is integration of the proviral
cDNA into human DNA. The selection of
chromosomal targets for integration is crucial for efficient viral
replication, but the mechanism is poorly
understood. Here we describe mapping of 524 sites of HIV
cDNA integration on the human genome sequence. Genes were found to be strongly
favored as integration acceptor sites. Global analysis of cellular transcription
indicated that active genes were preferential integration
targets, particularly genes that were activated in cells
after infection by HIV-1. Regional hotspots for integration
were also found, including a 2.4 kb region containing
1% of sites. These data document unexpectedly strong biases in integration
site selection and suggest how selective targeting promotes aggressive
HIV replication.
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