原创力文档retroviral dna integration aslv, hiv, and mlv show distinct target site preferences逆转录病毒dna整合alsv、艾滋病毒和mlv显示不同的目标站点首选项.pdfVIP
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retroviral dna integration aslv, hiv, and mlv show distinct target site preferences逆转录病毒dna整合alsv、艾滋病毒和mlv显示不同的目标站点首选项
Open access, freely available online PLoS BIOLOGY
Retroviral DNA Integration:
ASLV, HIV, and MLV Show
Distinct Target Site Preferences
1[ 1[ 2 3 3 4
Rick S. Mitchell , Brett F. Beitzel , Astrid R. W. Schroder , Paul Shinn , Huaming Chen , Charles C. Berry ,
3 1*
Joseph R. Ecker , Frederic D. Bushman
1 Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America, 2 Gen-Probe, San Diego, California,
United States of America, 3 Genomic Analysis Laboratory, The Salk Institute, La Jolla, California, United States of America, 4 Department of Family/Preventive Medicine,
University of California at San Diego School of Medicine, San Diego, California, United States of America
The completion of the human genome sequence has made possible genome-wide studies of retroviral DNA
integration. Here we report an analysis of 3,127 integration site sequences from human cells. We compared retroviral
vectors derived from human immunodeficiency virus (HIV), avian sarcoma-leukosis virus (ASLV), and murine leukemia
virus (MLV). Effects of gene activity on integration targeting were assessed by transcriptional profiling of infected cells.
Integration by HIV vectors, analyzed in two primary cell types and several cell lines, strongly favored active genes. An
analysis of the effects of tissue-specific transcription showed that it resulted in tissue-specific integration targeting by
HIV, though the effect was quantitatively modest. Chromosomal regions rich in expressed genes were favored for HIV
integration, but these regions were found to be interleaved with unfavora
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