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Journal of Virology, June 2004, p. 6122-6133, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6122-6133.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Resting CD4+ T Cells from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes

Yefei Han,1,{dagger} Kara Lassen,1,{dagger} Daphne Monie,1 Ahmad R. Sedaghat,1 Shino Shimoji,1 Xiao Liu,1 Theodore C. Pierson,1 Joseph B. Margolick,2 Robert F. Siliciano,1,3* and Janet D. Siliciano1

Department of Medicine, School of Medicine,1 Department of Molecular Microbiology and Immunology, School of Public Health, Johns Hopkins University,2 Howard Hughes Medical Institute, Baltimore, Maryland 212053

Received 19 January 2004/ Accepted 17 February 2004

Resting CD4+ T-cell populations from human immunodeficiency virus type 1 (HIV-1)-infected individuals include cells with integrated HIV-1 DNA. In individuals showing suppression of viremia during highly active antiretroviral therapy (HAART), resting CD4+ T-cell populations do not produce virus without cellular activation. To determine whether the nonproductive nature of the infection in resting CD4+ T cells is due to retroviral integration into chromosomal regions that are repressive for transcription, we used inverse PCR to characterize the HIV-1 integration sites in vivo in resting CD4+ T cells from patients on HAART. Of 74 integration sites from 16 patients, 93% resided within transcription units, usually within introns. Integration was random with respect to transcriptional orientation relative to the host gene and with respect to position within the host gene. Of integration sites within well-characterized genes, 91% (51 of 56) were in genes that were actively expressed in resting CD4+ T cells, as directly demonstrated by reverse transcriptase PCR (RT-PCR). These results predict that HIV-1 sequences may be included in the primary transcripts of host genes as part of rapidly degraded introns. RT-PCR experiments confirmed the presence of HIV-1 sequences within transcripts initiating upstream of the HIV-1 transcription start site. Taken together, these results demonstrate that HIV-1 genomes reside within actively transcribed host genes in resting CD4+ T cells in vivo.

* Corresponding author. Mailing address: Department of Medicine, Ross 1049, School of Medicine, Johns Hopkins University, 720 Rutland Ave., Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (443) 287-6218. E-mail: rsiliciano{at}jhmi.edu.

{dagger} Y.H. and K.L. contributed equally to this work.

Journal of Virology, June 2004, p. 6122-6133, Vol. 78, No. 12
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.12.6122-6133.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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