title: A novel action of minocycline: inhibition of human immunodeficiency virus type 1 infection in microglia.
abstract: Human immunodeficiency virus type 1 (HIV-1) infection of the brain produces a characteristic disease called acquired immunodeficiency syndrome (AIDS) dementia in which productive infection and inflammatory activation of microglia and macrophages play a central role. In this report, the authors demonstrate that minocycline (MC), a second-generation tetracycline with proven safety and penetration to the central nervous system, potently inhibited viral production from microglia. Inhibition of viral release was sustained through the entire course of infection and even when the drug exposure was limited to the first day of infection. Minocycline was effective even at low viral doses, and against R5- and X4R5-HIV, as well as in single-cycle reporter virus assays. Electrophoretic mobility shift analysis showed that minocycline inhibited nuclear factor (NF)-kappaB activation in microglia. HIV-1 long terminal repeat (LTR)-promoter activity in U38 cells was also inhibited. These results, combined with recently demonstrated in vivo anti-inflammatory effects of MC on microglia, suggest a potential utility for MC as an effective adjunct therapy for AIDS dementia.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Qiusheng
authors.initials: Q
authors.lastname: Si
authors.forename: Melissa
authors.initials: M
authors.lastname: Cosenza
authors.forename: Mee-Ohk
authors.initials: MO
authors.lastname: Kim
authors.forename: Meng-Liang
authors.initials: ML
authors.lastname: Zhao
authors.forename: Michael
authors.initials: M
authors.lastname: Brownlee
authors.forename: Harris
authors.initials: H
authors.lastname: Goldstein
authors.forename: Sunhee
authors.initials: S
authors.lastname: Lee
mesh_terms: D018929:Cell Culture Techniques; D016325:HIV Long Terminal Repeat; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D017628:Microglia / Q000187:drug effects* / Q000821:virology; D008911:Minocycline / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D016328:NF-kappa B; D008911:Minocycline