Neurokinin-1 receptor antagonist (aprepitant) suppresses HIV-1 infection of microglia/macrophages.
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 (< or =20%) had little effect on the anti-HIV-1 activity of aprepitant in macrophages. These observations provide additional evidence to support the potential use of NK-1R antagonists as therapeutic and immunomodulatory agents for the treatment of HIV-1 infection.
Wang
Xu
X
Department of Pediatrics, Joseph Stokes, Jr. Research Institute at The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Douglas
Steven D
SD
Song
Li
L
Wang
Yan-Jian
YJ
Ho
Wen-Zhe
WZ
D000998:Antiviral Agents / Q000494:pharmacology*; D000077608:Aprepitant; D002478:Cells, Cultured; D004357:Drug Synergism; D000077560:Enfuvirtide; D005434:Flow Cytometry; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000821:virology; D017628:Microglia / Q000187:drug effects* / Q000821:virology; D009025:Morpholines / Q000494:pharmacology*; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D009025:Morpholines; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D000077560:Enfuvirtide; D000077608:Aprepitant