Thalidomide and thalidomide analogs reduce HIV type 1 replication in human macrophages in vitro.
Thalidomide is currently being evaluated for efficacy in alleviating some manifestations of HIV-1 infection. To determine whether thalidomide has any direct effects on HIV-1 infection, we investigated the effect of thalidomide and also of three structural analogs of thalidomide on HIV-1 replication in vitro in human monocyte-derived macrophages. The thalidomide analogs were previously shown to inhibit TNF-alpha production in vitro at much lower concentrations than thalidomide. In HIV-1-infected macrophages treated with thalidomide or thalidomide analogs, viral replication was reduced by 60 to 80% as determined by measuring viral RT activity in the culture supernatants. In all experiments the analogs inhibited HIV-1 replication more efficiently than did thalidomide. The drugs also reduced HIV-1 gag mRNA expression. Furthermore, the drugs caused a decrease in NF-kappaB-binding activity in nuclear extracts of HIV-1-infected macrophages. The role of NF-kappaB in the drug-induced inhibition of HIV-1 replication was confirmed using an NF-kappaB-defective mutant virus to infect macrophages.
Moreira
A L
AL
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021, USA.
Corral
L G
LG
Ye
W
W
Johnson
B
B
Stirling
D
D
Muller
G W
GW
Freedman
V H
VH
Kaplan
G
G
D019380:Anti-HIV Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D015750:Genes, gag / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D012367:RNA, Viral; D013792:Thalidomide; D054303:HIV Reverse Transcriptase