@article{0c9cd46d446c48169e6e64f0ccce51d4,
title = "CD8+T cells fail to limit SIV reactivation following ART withdrawal until after viral amplification",
abstract = "To define the contribution of CD8+ T cell responses to control of SIV reactivation during and following antiretroviral therapy (ART), we determined the effect of long-term CD8+ T cell depletion using a rhesusized anti-CD8β monoclonal antibody on barcoded SIVmac239 dynamics on stable ART and after ART cessation in rhesus macaques (RMs). Among the RMs with full CD8+ T cell depletion in both blood and tissue, there were no significant differences in the frequency of viral blips in plasma, the number of SIV RNA+ cells and the average number of RNA copies/infected cell in tissue, and levels of cell-associated SIV RNA and DNA in blood and tissue relative to control-treated RMs during ART. Upon ART cessation, both CD8+ T cell-depleted and control RMs rebounded in fewer than 12 days, with no difference in the time to viral rebound or in either the number or growth rate of rebounding SIVmac239M barcode clonotypes. However, effectively CD8+ T cell-depleted RMs showed a stable, approximately 2-log increase in post-ART plasma viremia relative to controls. These results indicate that while potent antiviral CD8+ T cell responses can develop during ART-suppressed SIV infection, these responses effectively intercept post-ART SIV rebound only after systemic viral replication, too late to limit reactivation frequency or the early spread of reactivating SIV reservoirs.",
author = "Okoye, {Afam A.} and Duell, {Derick D.} and Yoshinori Fukazawa and Benjamin Varco-Merth and Alejandra Marenco and Hannah Behrens and Morgan Chaunzwa and Selseth, {Andrea N.} and Gilbride, {Roxanne M.} and Jason Shao and Edlefsen, {Paul T.} and Romas Geleziunas and Mykola Pinkevych and Davenport, {Miles P.} and Kathleen Busman-Sahay and Michael Nekorchuk and Haesun Park and Jeremy Smedley and Axthelm, {Michael K.} and Estes, {Jacob D.} and Hansen, {Scott G.} and Keele, {Brandon F.} and Lifson, {Jeffery D.} and Picker, {Louis J.}",
note = "Funding Information: This work was supported by grants from the NIH to LJP (grants UM1AI126611, UM1AI124377, 4R37AI054292) and to the Oregon National Primate Research Center (P51OD011092), by federal funds to JDL and BFK from the National Cancer Institute, NIH (contracts HHSN261200800001E and 75N91019D00024), and by an NIH grant to JDE for the Integrated Pathology Core at the Oregon National Primate Research Center (grant 1S10OD025002-01). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The CD8β-depleting mAb CD8β255R1 and IgG isotype control mAbs were provided by the NIH Nonhuman Primate Reagent Resource Program. Tetramers were provided by the NIH Tetramer Core Facility at Emory University and ART drugs were provided by Gilead Sciences Inc. We thank the Quantitative Molecular Diagnostics Core of the AIDS and Cancer Virus Program of the Frederick National Laboratory for viral load analyses. We also thank A. Sylwester, S. Hagen, T. Swanson, M. Fischer, C. Shriver-Munsch, E. McDonald, K., W. Brantley, R. Lum, A. Maxwell, M. Lidell, D. Morrow, J. Ford, A. Townsend, and K. Rothstein for technical and/or administrative assistance. Publisher Copyright: {\textcopyright} 2021, American Society for Clinical Investigation.",
year = "2021",
month = apr,
day = "15",
doi = "10.1172/JCI141677",
language = "English (US)",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "8",
}