期刊
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
卷 3, 期 4, 页码 257-264出版社
SPRINGER
DOI: 10.1007/s11481-008-9117-3
关键词
aprepitant; macrophage; HIV-1; neurokinin 1 receptor
资金
- National Institutes of Health [DA-012815, DA-022177, PO1 MH 076388, PO1 MH 049981]
- NATIONAL INSTITUTE OF MENTAL HEALTH [P01MH076388, R01MH049981] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA012815, R21DA025477, R01DA022177] Funding Source: NIH RePORTER
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 (<= 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.
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