Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children

Bale, M. J.; Katusiime, M. G.; Wells, D.; Wu, X.; Spindler, J.; Halvas, E. K.; Cyktor, J. C.; Wiegand, A.; Shao, W.; Cotton, M. F.; Hughes, S. H.; Mellors, J. W.; Coffin, J. M.; Van Zyl, G. U.; Kearney, M. F.

doi:10.1101/2020.09.15.298406

bioRxiv · 10.1101/2020.09.15.298406

Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children

Bale, M. J.·Katusiime, M. G.·Wells, D.·Wu, X.·Spindler, J.·Halvas, E. K.·Cyktor, J. C.·Wiegand, A.·Shao, W.·Cotton, M. F.·Hughes, S. H.·Mellors, J. W.·Coffin, J. M.·Van Zyl, G. U.·Kearney, M. F.

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Abstract

Little is known about the emergence and persistence of HIV-infected T cell clones in perinatally-infected children. We analyzed peripheral blood mononuclear cells for clonal expansion in 11 children who initiated antiretroviral therapy (ART) between 1.8-17.4 months of age and with viremia suppressed for 6-9 years. We obtained 8,662 HIV-1 integration sites from pre-ART and 1,861 sites on ART. Expanded clones of infected cells were detected pre-ART in 10/11 children. In 8 children, infected cell clones detected pre-ART persisted for 6-9 years on ART. A comparison of integration sites in the samples obtained on ART with healthy donor PBMC infected ex-vivo showed selection for cells with proviruses integrated in BACH2 and STAT5B. Our analyses indicate that, despite marked differences in T cell composition and dynamics between children and adults, HIV-infected cell clones are established early in children, persist for up to 9 years on ART, and can be driven by proviral integration in proto-oncogenes.

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Bale, M. J., Katusiime, M. G., Wells, D., Wu, X., Spindler, J., Halvas, E. K., Cyktor, J. C., Wiegand, A., Shao, W., Cotton, M. F., Hughes, S. H., Mellors, J. W., Coffin, J. M., Van Zyl, G. U., Kearney, M. F.. 2020-09-15. Early Emergence and Long-Term Persistence of HIV-Infected T Cell Clones in Children. https://doi.org/10.1101/2020.09.15.298406

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