Minocycline Attenuates HIV Infection and Reactivation by Suppressing Cellular Activation in Human CD4+ T Cells

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2010 Mar 9

PMID 20205570

Citations 35

Authors

Gregory L Szeto

Angela K Brice

Hung-Chih Yang

Sheila A Barber

Robert F Siliciano

Janice E Clements

Affiliations

Soon will be listed here.

Abstract

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.

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References

Zhang Y, Metz L, Yong V, Bell R, Yeung M, Patry D . Pilot study of minocycline in relapsing-remitting multiple sclerosis. Can J Neurol Sci. 2008; 35(2):185-91. DOI: 10.1017/s0317167100008611. View

Daoud A, Gloria C, Taningco G, Hammerschlag M, Weiss S, Gelling M . Minocycline treatment results in reduced oral steroid requirements in adult asthma. Allergy Asthma Proc. 2008; 29(3):286-94. DOI: 10.2500/aap.2008.29.3121. View

dArminio Monforte A, Lepri A, Rezza G, Pezzotti P, Antinori A, Phillips A . Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients. AIDS. 2000; 14(5):499-507. DOI: 10.1097/00002030-200003310-00005. View

Sakellari D, Goodson J, Kolokotronis A, Konstantinidis A . Concentration of 3 tetracyclines in plasma, gingival crevice fluid and saliva. J Clin Periodontol. 2000; 27(1):53-60. DOI: 10.1034/j.1600-051x.2000.027001053.x. View

Yang H, Xing S, Shan L, OConnell K, Dinoso J, Shen A . Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation. J Clin Invest. 2009; 119(11):3473-86. PMC: 2769176. DOI: 10.1172/JCI39199. View

Alarcon G . Tetracyclines for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs. 2000; 9(7):1491-8. DOI: 10.1517/13543784.9.7.1491. View

Chougnet C, Freitag C, Schito M, Thomas E, Sher A, Shearer G . In vivo CD40-CD154 (CD40 ligand) interaction induces integrated HIV expression by APC in an HIV-1-transgenic mouse model. J Immunol. 2001; 166(5):3210-7. DOI: 10.4049/jimmunol.166.5.3210. View

ODell J, Blakely K, Mallek J, Eckhoff P, Leff R, Wees S . Treatment of early seropositive rheumatoid arthritis: a two-year, double-blind comparison of minocycline and hydroxychloroquine. Arthritis Rheum. 2001; 44(10):2235-41. DOI: 10.1002/1529-0131(200110)44:10<2235::aid-art385>3.0.co;2-a. View

Veazey R, Ling B, Pandrea I, McClure H, Lackner A, Marx P . Decreased CCR5 expression on CD4+ T cells of SIV-infected sooty mangabeys. AIDS Res Hum Retroviruses. 2003; 19(3):227-33. DOI: 10.1089/088922203763315731. View

10.

Zhang H, Zhou Y, Alcock C, Kiefer T, Monie D, Siliciano J . Novel single-cell-level phenotypic assay for residual drug susceptibility and reduced replication capacity of drug-resistant human immunodeficiency virus type 1. J Virol. 2004; 78(4):1718-29. PMC: 369469. DOI: 10.1128/jvi.78.4.1718-1729.2004. View

11.

Neckers L, Cossman J . Transferrin receptor induction in mitogen-stimulated human T lymphocytes is required for DNA synthesis and cell division and is regulated by interleukin 2. Proc Natl Acad Sci U S A. 1983; 80(11):3494-8. PMC: 394071. DOI: 10.1073/pnas.80.11.3494. View

12.

McDougal J, Mawle A, Cort S, Nicholson J, Cross G, Hicks D . Cellular tropism of the human retrovirus HTLV-III/LAV. I. Role of T cell activation and expression of the T4 antigen. J Immunol. 1985; 135(5):3151-62. View

13.

Luciw P, Peterlin B . Human immunodeficiency virus long terminal repeat responds to T-cell activation signals. Proc Natl Acad Sci U S A. 1987; 84(19):6845-9. PMC: 299181. DOI: 10.1073/pnas.84.19.6845. View

14.

Cebrian M, Yague E, Rincon M, Lopez-Botet M, de Landazuri M, Sanchez-Madrid F . Triggering of T cell proliferation through AIM, an activation inducer molecule expressed on activated human lymphocytes. J Exp Med. 1988; 168(5):1621-37. PMC: 2189112. DOI: 10.1084/jem.168.5.1621. View

15.

Saivin S, Houin G . Clinical pharmacokinetics of doxycycline and minocycline. Clin Pharmacokinet. 1988; 15(6):355-66. DOI: 10.2165/00003088-198815060-00001. View

16.

Duh E, Maury W, Folks T, Fauci A, Rabson A . Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci U S A. 1989; 86(15):5974-8. PMC: 297754. DOI: 10.1073/pnas.86.15.5974. View

17.

Stevenson M, Stanwick T, Dempsey M, Lamonica C . HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J. 1990; 9(5):1551-60. PMC: 551849. DOI: 10.1002/j.1460-2075.1990.tb08274.x. View

18.

Li Y, Mak G, Franza Jr B . In vitro study of functional involvement of Sp1, NF-kappa B/Rel, and AP1 in phorbol 12-myristate 13-acetate-mediated HIV-1 long terminal repeat activation. J Biol Chem. 1994; 269(48):30616-9. View

19.

Kloppenburg M, Verweij C, Miltenburg A, Verhoeven A, Daha M, Dijkmans B . The influence of tetracyclines on T cell activation. Clin Exp Immunol. 1995; 102(3):635-41. PMC: 1553388. DOI: 10.1111/j.1365-2249.1995.tb03864.x. View

20.

Kloppenburg M, Brinkman B, Miltenburg A, Daha M, Breedveld F, Dijkmans B . The tetracycline derivative minocycline differentially affects cytokine production by monocytes and T lymphocytes. Antimicrob Agents Chemother. 1996; 40(4):934-40. PMC: 163234. DOI: 10.1128/AAC.40.4.934. View