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

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Laforge, M (Author) Other; Silvestre, R (Author) Other; Rodrigues, V (Author) Other; Garibal, J (Author) Other; Campillo Gimenez, L (Author) Other; Mouhamad, S (Author) Other; Monceaux, V (Author) Other; Cumont, MC (Author) Other; Rabezanahary, H (Author) Other; Pruvost, A (Author) Other; Anabela Cordeiro da Silva (Author) FFUP; Hurtrel, B (Author) Other; Silvestri, G (Author) Other; Senik, A (Author) Other; Estaquier, J (Author) Other

Journal

Title: Journal of Clinical Investigation

Vol. 128

Pages: 1627-1640

ISSN: 0021-9738

Publisher: American Society for Clinical Investigation

Indexing

ISI Web of Knowledge - 4 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-00N-VS6

DOI: 10.1172/jci95127

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14