Journal Article

Recurrent HIV-1 Integration at the <i>BACH2</i> Locus in Resting CD4<sup>+</sup> T Cell Populations during Effective Highly Active Antiretroviral Therapy

Terumasa Ikeda, Junji Shibata, Kazuhisa Yoshimura, Atsushi Koito and Shuzo Matsushita

in The Journal of Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 195, issue 5, pages 716-725
Published in print March 2007 | ISSN: 0022-1899
Published online March 2007 | e-ISSN: 1537-6613 | DOI: https://dx.doi.org/10.1086/510915
Recurrent HIV-1 Integration at the BACH2 Locus in Resting CD4+ T Cell Populations during Effective Highly Active Antiretroviral Therapy

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The persistence of latent human immunodeficiency virus type 1 (HIV-1) has been considered one of the major obstacles for eradication of the virus in infected individuals receiving successful antiretroviral therapy. To determine the contribution of integration sites to viral latency within clinical settings, an inverse polymerase chain reaction method was used to analyze integration sites in CD4+ T cells from patients showing long-term undetectable plasma viral RNA. Of 457 sites identified in 7 patients, almost all (96%) resided within transcriptional units, usually in introns of the human genome. Studies of 18 genes in which HIV-1 integrates found them to be actively expressed in resting CD4+ T cells. On the other hand, integration sites in the α satellite region was also identified in some patients, albeit at low frequency. Of particular interest, HIV-1-infected cells with multiple identical integration sites were detected in longitudinal analysis of samples from 3 patients, suggesting that these cells persist for long periods and that clonal expansion may occur. Furthermore, strong integration clusters in the BACH2 gene were observed in 2 patients (31% in patient 1 and 5% in patient 3). Our findings not only raise the possibility of biased target-site integration but also provide mechanistic insights into the long-term persistence of HIV-1.

Journal Article.  5146 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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