Article (Scientific journals)
The RIAD peptidomimetic inhibits HIV-1 replication in humanized NSG mice
Singh, Maneesh; Singh, Pratibha; VAIRA, Dolorès et al.
2014In European Journal of Clinical Investigation, 44 (2), p. 146-152
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Keywords :
cAMP; HIV; NOD/LtsZ-scidIL-2Rcnull mice; RIAD peptidomimetic
Abstract :
[en] Background Increased intracellular concentration of cyclic AMP (cAMP) in T cells is associated with various immunodeficiency conditions including human immunodeficiency virus (HIV) infection. Several reports indicate a critical role of activated protein kinase A (PKA) in the susceptibility of cells to HIV infection. We have used a cell permeable, stable peptidomimetic version (P3) of the RI-anchoring disruptor (RIAD), which prevents PKA interaction with A-kinase-anchoring proteins (AKAPs). It is known that RIAD peptide abrogates effects of localized cAMP signalling through anchored type I PKA in lymphocytes and prevents murine AIDS (MAIDS) infection when expressed as a transgene in mice. Methods and Results In vitro HIV-infected human peripheral blood mononuclear cells (PBMCs) show reduced levels of p24 and intracellular cAMP in T cells when treated with RIAD peptidomimetic (RIAD-P3). Humanized NOD/SCID/IL2cnull (NSG) mice infected with HIV-1 JRCSF and treated with RIAD-P3 (3􏰀5 mg) once every 2 weeks showed significantly reduced levels of viral load at +28, +42 and +56 days and increased CD4 numbers at +56 days after the start of treatment. RIAD-P3-treated humanized mice had lower levels of intracellular cAMP in T cells sorted from splenocytes. Conclusions Treatment with RIAD-P3 limits HIV-1 viral replication and stabilizes CD4 levels by mechanisms involving cAMP/PKA-I pathway in human PBMCs and humanized NSG mice.
Disciplines :
Immunology & infectious disease
Author, co-author :
Singh, Maneesh
Singh, Pratibha
VAIRA, Dolorès ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - LRS Biomol
Torheim, Eirik A.
Rahmouni, Souad  ;  Université de Liège - ULiège > Département des sciences cliniques > GIGA-R:Immunopath. - Maladies infect. et médec. inter. gén.
Tasken, Kjetil
MOUTSCHEN, Michel  ;  Centre Hospitalier Universitaire de Liège - CHU > Maladies infectieuses et médecine interne générale
Language :
Title :
The RIAD peptidomimetic inhibits HIV-1 replication in humanized NSG mice
Publication date :
February 2014
Journal title :
European Journal of Clinical Investigation
Publisher :
Blackwell Publishing, Oxford, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
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