Details

Autor(en) / Beteiligte

• Laforge, Mireille
• Silvestre, Ricardo
• Rodrigues, Vasco
• Garibal, Julie
• Campillo-Gimenez, Laure
• Mouhamad, Shahul
• Monceaux, Valérie
• Cumont, Marie-Christine
• Rabezanahary, Henintsoa
• Pruvost, Alain
• Cordeiro-da-Silva, Anabela
• Hurtrel, Bruno
• Silvestri, Guido
• Senik, Anna
• Estaquier, Jérôme

Titel

The anti-caspase inhibitor Q-VD-OPH prevents AIDS disease progression in SIV-infected rhesus macaques

Ist Teil von

• The Journal of clinical investigation, 2018-04, Vol.128 (4), p.1627-1640

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Apoptosis has been proposed as a key mechanism responsible for CD4+ T cell depletion and immune dysfunction during HIV infection. We demonstrated that Q-VD-OPH, a caspase inhibitor, inhibits spontaneous and activation-induced death of T cells from SIV-infected rhesus macaques (RMs). When administered during the acute phase of infection, Q-VD-OPH was associated with (a) reduced levels of T cell death, (b) preservation of CD4+/CD8+ T cell ratio in lymphoid organs and in the gut, (c) maintenance of memory CD4+ T cells, and (d) increased specific CD4+ T cell response associated with the expression of cytotoxic molecules. Although therapy was limited to the acute phase of infection, Q-VD-OPH-treated RMs showed lower levels of both viral load and cell-associated SIV DNA as compared with control SIV-infected RMs throughout the chronic phase of infection, and prevented the development of AIDS. Overall, our data demonstrate that Q-VD-OPH injection in SIV-infected RMs may represent an adjunctive therapeutic agent to control HIV infection and delaying disease progression to AIDS.