A novel action of minocycline: Inhibition of human immunodeficiency virus type 1 infection in microglia

• Published in: Journal of neurovirology Vol. 10; no. 5; pp. 284 - 292
• Main Authors: Si, Qiusheng, Cosenza, Melissa A, Kim, Mee-Ohk, Zhao, Meng-Liang, Brownlee, Michael, Goldstein, Harris, Lee, Sunhee C
• Format: Journal Article
• Language: English
• Published: London Informa UK Ltd 01.10.2004; Taylor & Francis
• Subjects: Biological and medical sciences; Cell Culture Techniques; HIV Long Terminal Repeat; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - physiology; Human immunodeficiency virus 1; Human viral diseases; Humans; Infectious diseases; Medical sciences; Microglia - drug effects; Microglia - virology; Minocycline - pharmacology; NF-kappa B - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Virus Replication - drug effects; Immunopathology; Nervous system diseases; HIV-1 virus; Neuroglia; Central nervous system; Retroviridae; AIDS; Inflammation; brain; Immune deficiency; Lentivirus; Encephalon; Microglia; Tetracycline; Infection; Virus; NF-κB; HIV; Viral disease; Minocycline; Human immunodeficiency virus; Dementia
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1080/13550280490499533

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)-κ B 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.