Minocycline attenuates HIV infection and reactivation by suppressing cellular activation in human CD4+ T cells.
Treatment of human immunodeficiency virus (HIV) infection with highly active antiretroviral therapy (HAART) is effective but can be associated with toxic effects and is expensive. Other options may be useful for long-term therapy. The immunomodulatory antibiotic minocycline could be an effective, low-cost adjunctive treatment to HAART. Minocycline mediated a dose-dependent decrease in single-cycle CXCR4-tropic HIV infection and decreased viral RNA after infection of CD4+ T cells with HIV NL4-3. Reactivation from latency was also decreased in a primary CD4+ T cell-derived model and in resting CD4+ T cells from HIV-infected patients. Minocycline treatment resulted in significant changes in activation marker expression and inhibited proliferation and cytokine secretion of CD4+ T cells in response to activation. This study demonstrates that minocycline reduces HIV replication and reactivation and decreases CD4+ T cell activation. The anti-HIV effects of minocycline are mediated by altering the cellular environment rather than directly targeting virus, placing minocycline in the class of anticellular anti-HIV drugs.
Szeto
Gregory L
GL
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Brice
Angela K
AK
Yang
Hung-Chih
HC
Barber
Sheila A
SA
Siliciano
Robert F
RF
Clements
Janice E
JE
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects*; D002472:Cell Transformation, Viral / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008911:Minocycline / Q000494:pharmacology* / Q000627:therapeutic use; D012367:RNA, Viral / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D017735:Virus Latency / Q000187:drug effects
D019380:Anti-HIV Agents; D016207:Cytokines; D004279:DNA, Viral; D012367:RNA, Viral; D008911:Minocycline