Bibliographic Details
| Title: |
Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques. |
| Authors: |
Pino, Maria, Pagliuzza, Amélie, Pampena, M. Betina, Deleage, Claire, Viox, Elise G., Nguyen, Kevin, Shim, Inbo, Zhang, Adam, Harper, Justin L., Samer, Sadia, King, Colin T., Cervasi, Barbara, Gill, Kiran P., Ehnert, Stephanie, Jean, Sherrie M., Freeman, Michael L., Lifson, Jeffrey D., Kulpa, Deanna, Betts, Michael R., Chomont, Nicolas |
| Source: |
Nature Communications; 8/27/2022, Vol. 13 Issue 1, p1-12, 12p |
| Subject Terms: |
RHESUS monkeys, T helper cells, LYMPHOID tissue, FINGOLIMOD, KILLER cells, HIV-positive persons, PLASMA frequencies |
| Abstract: |
Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes. This increase of cytolytic cells, however, does not limit measures of viral persistence during ART, including intact proviral genomes. After ART interruption, a subset of animals that initially receives FTY720 displays a modest delay in viral rebound, with reduced plasma viremia and frequencies of infected T follicular helper cells. Further research is needed to optimize the potential utility of FTY720 when coupled with strategies that boost the antiviral function of T-cells in lymphoid tissues. Although antiretroviral therapy (ART) is able to successfully suppress plasma viremia in most people living with HIV, ART withdrawal typically results in viral replication and rebound. Authors investigate the effect, in terms of delay in viral replication, and immune cell dynamics in lymphoid tissue, of fingolimod (FTY720) administration at the time of ART initiation in SIV-infected rhesus macaques. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
