Resting CD4+T Cells from Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Individuals Carry Integrated HIV-1 Genomes within Actively Transcribed Host Genes
- 15 June 2004
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 78 (12), 6122-6133
- https://doi.org/10.1128/jvi.78.12.6122-6133.2004
Abstract
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.Keywords
This publication has 66 references indexed in Scilit:
- HIV-1 Nef intersects the macrophage CD40L signalling pathway to promote resting-cell infectionNature, 2003
- The establishment and maintenance of lymphocyte identity through gene silencingNature Immunology, 2003
- Interleukin-7 Induces Expression of Latent Human Immunodeficiency Virus Type 1 with Minimal Effects on T-Cell PhenotypeJournal of Virology, 2002
- Induction of TAK (Cyclin T1/P-TEFb) in Purified Resting CD4 + T Lymphocytes by Combination of CytokinesJournal of Virology, 2001
- Genomic and Genetic Definition of a Functional Human CentromereScience, 2001
- Initial sequencing and analysis of the human genomeNature, 2001
- Sexual Transmission and Propagation of SIV and HIV in Resting and Activated CD4 + T CellsScience, 1999
- Quantification of latent tissue reservoirs and total body viral load in HIV-1 infectionNature, 1997
- Tissue Distribution and Abundance of Human FKBP51, an FK506-Binding Protein That Can Mediate Calcineurin InhibitionBiochemical and Biophysical Research Communications, 1997
- CONTROL OF RNA INITIATION AND ELONGATION AT THE HIV-1 PROMOTERAnnual Review of Biochemistry, 1994