Neurokinin-1 Receptor Antagonist (Aprepitant) Suppresses HIV-1 Infection of Microglia/Macrophages

TitleNeurokinin-1 Receptor Antagonist (Aprepitant) Suppresses HIV-1 Infection of Microglia/Macrophages
Publication TypeJournal Article
Year of Publication2008
AuthorsWang, X, Douglas, SD, Song, L, Wang, Y, Ho, WZ
JournalJournal of Neuroimmune Pharmacology
Date Published2008
KeywordsExternal
Abstract

Neurokinin-1 receptor (NK-1R) antagonists suppress HIV-1 infection of macrophages in vitro. We have further investigated the anti-HIV-1 activity of aprepitant, a Food and Drug Administration-approved NK-1R antagonist, and its cytotoxic effect in the macrophage/microglia system. Aprepitant inhibited infection of macrophages with primary HIV-1 R5 strains (subtypes A, D, and H; UG275, BZ163, and BCF-KITA), while it had little effect on primary HIV-1 X4 strains (subtypes B and D, BZ167 and SE365). Aprepitant, when added to microglia cultures infected with CSF-derived HIV-1 strains (JAGO or JRFL), significantly inhibited viral replication. Aprepitant also enhanced the anti-HIV-1 activity of enfuvirtide (an HIV-1 fusion inhibitor) in HIV-1-infected macrophages. Over a concentration range of 10(-9) to 10(-5) M, aprepitant had little cytotoxic effect (less than 10%) on macrophages during the in vitro cultures. Autologous human serum (

URLhttp://www.ncbi.nlm.nih.gov/pubmed/18654860