Early Emergence and Long-Term Persistence of HIV-Infected T-Cell Clones in Children
Michael J. Bale, Mary Grace Katusiime, Daria Wells, Xiaolin Wu, Jonathan Spindler, Elias K. Halvas, Joshua C. Cyktor, Ann Wiegand, Wei Shao, Mark F. Cotton, Stephen H. Hughes, John W. Mellors, John M. Coffin, Gert U. van Zyl, Mary F. Kearney
Abstract
HIV-1 integrates its genome into the DNA of host cells. Consequently, HIV-1 genomes are copied with the host cell DNA during cellular division. Pediatric immune systems differ significantly from adults, consisting primarily of naive T cells, which have low expression of the HIV-1 coreceptor CCR5. This difference may result in variances in the number or size of infected cell clones that persist in children on ART. Here, we provide the most extensive analysis of the integration landscape of HIV-1 in children. We found that, despite the largely naive cell populations in neonatal immune systems, patterns of HIV-1 integration and the size of infected cell clones are as large and widespread as those in adults. Furthermore, selection for integration events in proto-oncogenes were observed in children despite early ART. If such cell clones persist for the life span of these individuals, there may be long-term consequences that have yet to be realized.