Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure
Antiretroviral therapy regimens durably suppress HIV replication, but do not cure infection. This is partially attributable to the persistence of long-lived pools of resting CD4+ T-cells harboring latent replication-competent virus. Substantial clinical and pre-clinical research is currently being d...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2018.01452/full |
| _version_ | 1811270312908554240 |
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| author | Genevieve Tyndale Clutton R. Brad Jones R. Brad Jones |
| author_facet | Genevieve Tyndale Clutton R. Brad Jones R. Brad Jones |
| author_sort | Genevieve Tyndale Clutton |
| collection | DOAJ |
| description | Antiretroviral therapy regimens durably suppress HIV replication, but do not cure infection. This is partially attributable to the persistence of long-lived pools of resting CD4+ T-cells harboring latent replication-competent virus. Substantial clinical and pre-clinical research is currently being directed at purging this viral reservoir by combining pharmacological latency reversal with immune effectors, such as HIV-specific CD8+ T-cells, capable of eliminating reactivated targets—the so-called “shock-and-kill” approach. However, several studies indicate that the latency-reversing agents (LRAs) may affect CD8+ T-cell function. The current review aims to frame recent advances, and ongoing challenges, in implementing “shock-and-kill” strategies from the perspective of effectively harnessing CD8+ T-cells. We review and contextualize findings indicating that LRAs often have unintended impacts on CD8+ T-cell function, both detrimental and beneficial. We identify and attempt to bridge the gap between viral reactivation, as measured by the detection of RNA or protein, and bona fide presentation of viral antigens to CD8+ T-cells. Finally, we highlight factors on the effector (CD8+) and target (CD4+) cell sides that contribute to whether or not infected-cell recognition results in killing/elimination. These perspectives may contribute to an integrated view of “shock-and-kill,” with implications for therapeutic development. |
| first_indexed | 2024-04-12T21:59:11Z |
| format | Article |
| id | doaj.art-93f6434356494177900ba0e0dfbbd71a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T21:59:11Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-93f6434356494177900ba0e0dfbbd71a2022-12-22T03:15:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01452384868Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV CureGenevieve Tyndale Clutton0R. Brad Jones1R. Brad Jones2Department of Microbiology and Immunology, UNC Chapel Hill School of Medicine, Chapel Hill, NC, United StatesDepartment of Microbiology Immunology and Tropical Medicine, The George Washington University, Washington, DC, United StatesInfectious Disease Division, Weill Cornell Medical College, New York, NY, United StatesAntiretroviral therapy regimens durably suppress HIV replication, but do not cure infection. This is partially attributable to the persistence of long-lived pools of resting CD4+ T-cells harboring latent replication-competent virus. Substantial clinical and pre-clinical research is currently being directed at purging this viral reservoir by combining pharmacological latency reversal with immune effectors, such as HIV-specific CD8+ T-cells, capable of eliminating reactivated targets—the so-called “shock-and-kill” approach. However, several studies indicate that the latency-reversing agents (LRAs) may affect CD8+ T-cell function. The current review aims to frame recent advances, and ongoing challenges, in implementing “shock-and-kill” strategies from the perspective of effectively harnessing CD8+ T-cells. We review and contextualize findings indicating that LRAs often have unintended impacts on CD8+ T-cell function, both detrimental and beneficial. We identify and attempt to bridge the gap between viral reactivation, as measured by the detection of RNA or protein, and bona fide presentation of viral antigens to CD8+ T-cells. Finally, we highlight factors on the effector (CD8+) and target (CD4+) cell sides that contribute to whether or not infected-cell recognition results in killing/elimination. These perspectives may contribute to an integrated view of “shock-and-kill,” with implications for therapeutic development.https://www.frontiersin.org/article/10.3389/fimmu.2018.01452/fullT-cellsHIV cureshock-and-killhistone deacetylase inhibitorPKCa |
| spellingShingle | Genevieve Tyndale Clutton R. Brad Jones R. Brad Jones Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure Frontiers in Immunology T-cells HIV cure shock-and-kill histone deacetylase inhibitor PKCa |
| title | Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure |
| title_full | Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure |
| title_fullStr | Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure |
| title_full_unstemmed | Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure |
| title_short | Diverse Impacts of HIV Latency-Reversing Agents on CD8+ T-Cell Function: Implications for HIV Cure |
| title_sort | diverse impacts of hiv latency reversing agents on cd8 t cell function implications for hiv cure |
| topic | T-cells HIV cure shock-and-kill histone deacetylase inhibitor PKCa |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2018.01452/full |
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