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Abstract
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.