Inhibition of HIV expression and integration in macrophages by methylglyoxal-bis-guanylhydrazone

Journal of Virology

Volumn 89, Issue 22, 2015, Pages 11176-11189

  Jin, Xia ^a   McGrath, Michael S ^b,c   Xu, Hua ^a  

^a Pathologica LLC   (United States)

^b UCSF Department of Medicine   (United States)

^c SAN FRANCISCO GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSYLMETHIONINE DECARBOXYLASE; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR5; ELVITEGRAVIR; ENHANCED GREEN FLUORESCENT PROTEIN; GAG PROTEIN; MITOGUAZONE; POLYAMINE; ANTIRETROVIRUS AGENT; CCR5 PROTEIN, HUMAN; GREEN FLUORESCENT PROTEIN; LIPOPOLYSACCHARIDE RECEPTOR;

ACTIVE TRANSPORT; ARTICLE; CELL ACTIVATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOTOXICITY; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IC50; LIFE CYCLE; MACROPHAGE; MONOCYTE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; VIRUS DNA CELL DNA INTERACTION; VIRUS INHIBITION; VIRUS ISOLATION; VIRUS REPLICATION; VIRUS STRAIN; BIOSYNTHESIS; CELL CULTURE; DRUG EFFECT; GENETICS; GROWTH, DEVELOPMENT AND AGING; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; METABOLISM; VIROLOGY;

ADENOSYLMETHIONINE DECARBOXYLASE; ANTI-RETROVIRAL AGENTS; BIOLOGICAL TRANSPORT, ACTIVE; CD4 ANTIGENS; CELLS, CULTURED; GREEN FLUORESCENT PROTEINS; HIV CORE PROTEIN P24; HIV INFECTIONS; HIV-1; HUMANS; LIPOPOLYSACCHARIDE RECEPTORS; MACROPHAGES; MITOGUAZONE; MONOCYTES; RECEPTORS, CCR5; VIRUS INTEGRATION; VIRUS REPLICATION;

EID: 84945970181     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01692-15     Document Type: Article

References (83)

1. Le Douce V, Herbein G, Rohr O, Schwartz C. 2010. Molecular mechanisms of HIV-1 persistence in the monocyte-macrophage lineage. Retrovirology 7:32. http://dx.doi.org/10.1186/1742-4690-7-32.
2. Geeraert L, Kraus G, Pomerantz RJ. 2008. Hide-and-seek: the challenge of viral persistence in HIV-1 infection. Annu Rev Med 59:487-501. http://dx.doi.org/10.1146/annurev.med.59.062806.123001.
3. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. 2009. The challenge of finding a cure for HIV infection. Science 323:1304-1307. http://dx.doi.org/10.1126/science.1165706.
4. Riva E, Antonelli G, Solmone MC, Turriziani O, Narciso P, Tozzi V, Dianzani F. 2000. Significant reduction in HIV-1 plasma viral load but not in proviral infected cells during sub-optimal antiretroviral therapy. J Biol Regul Homeost Agents 14:1-3.
5. Ibáñez A, Puig T, Elias J, Clotet B, Ruiz L, Martínez MA. 1999. Quantification of integrated and total HIV-1 DNA after long-term highly active antiretroviral therapy in HIV-1-infected patients. AIDS 13:1045-1049. http://dx.doi.org/10.1097/00002030-199906180-00007.
6. Zhang L, Chung C, Hu BS, He T, Guo Y, Kim AJ, Skulsky E, Jin X, Hurley A, Ramratnam B, Markowitz M, Ho DD. 2000. Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest 106:839-845. http://dx.doi.org/10.1172/JCI10565.
7. Harrigan PR, Whaley M, Montaner JS. 1999. Rate of HIV-1 RNA rebound upon stopping antiretroviral therapy. AIDS 13:F59-F62. http://dx.doi.org/10.1097/00002030-199905280-00001.
8. Alexaki A, Liu Y, Wigdahl B. 2008. Cellular reservoirs of HIV-1 and their role in viral persistence. Curr HIV Res 6:388-400. http://dx.doi.org/10.2174/157016208785861195.
9. Koppensteiner H, Brack-Werner R, Schindler M. 2012. Macrophages and their relevance in human immunodeficiency virus type I infection. Retrovirology 9:82. http://dx.doi.org/10.1186/1742-4690-9-82.
10. Siliciano RF, Greene WC. 2011. HIV latency. Cold Spring Harb Perspect Med 1:a007096. http://dx.doi.org/10.1101/cshperspect.a007096.
11. Shiramizu B, Gartner S, Williams A, Shikuma C, Ratto-Kim S, Watters M, Aguon J, Valcour V. 2005. Circulating proviral HIV DNA and HIVassociated dementia. AIDS 19:45-52. http://dx.doi.org/10.1097/00002030-200501030-00005.
12. Parrish NF, Gao F, Li H, Giorgi EE, Barbian HJ, Parrish EH, Zajic L, Iyer SS, Decker JM, Kumar A, Hora B, Berg A, Cai F, Hopper J, Denny TN, Ding H, Ochsenbauer C, Kappes JC, Galimidi RP, West AP, Jr, Bjorkman PJ, Wilen CB, Doms RW, O'Brien M, Bhardwaj N, Borrow P, Haynes BF, Muldoon M, Theiler JP, Korber B, Shaw GM, Hahn BH. 2013. Phenotypic properties of transmitted founder HIV-1. Proc Natl Acad Sci U S A 110:6626-6633. http://dx.doi.org/10.1073/pnas.1304288110.
13. Shen R, Richter HE, Clements RH, Novak L, HuffK, Bimczok D, Sankaran-Walters S, Dandekar S, Clapham PR, Smythies LE, Smith PD. 2009. Macrophages in vaginal but not intestinal mucosa are monocytelike and permissive to human immunodeficiency virus type 1 infection. J Virol 83:3258-3267. http://dx.doi.org/10.1128/JVI.01796-08.
14. Coleman CM, Wu L. 2009. HIV interactions with monocytes and dendritic cells: viral latency and reservoirs. Retrovirology 6:51. http://dx.doi.org/10.1186/1742-4690-6-51.
15. Philpott SM. 2003. HIV-1 coreceptor usage, transmission, and disease progression. Curr HIV Res 1:217-227. http://dx.doi.org/10.2174/1570162033485357.
16. Waki K, Freed EO. 2010. Macrophages and cell-cell spread of HIV-1. Viruses 2:1603-1620. http://dx.doi.org/10.3390/v2081603.
17. McDonald D, Wu L, Bohks SM, Kewal Ramani VN, Unutmaz D, Hope TJ. 2003. Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300:1295-1297. http://dx.doi.org/10.1126/science.1084238.
18. Granelli-Piperno A, Delgado E, Finkel V, Paxton W, Steinman RM. 1998. Immature dendritic cells selectively replicate macrophagetropic (Mtropic) human immunodeficiency virus type 1, while mature cells efficiently transmit both M-and T-tropic virus to T cells. J Virol 72:2733-2737.
19. Sharova N, Swingler C, Sharkey M, Stevenson M. 2005. Macrophages archive HIV-1 virions for dissemination in trans. EMBO J 24:2481-2489. http://dx.doi.org/10.1038/sj.emboj.7600707.
20. Ho DD, Rota TR, Hirsch MS. 1986. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest 77:1712-1715. http://dx.doi.org/10.1172/JCI112491.
21. Nicholson JK, Cross GD, Callaway CS, McDougal JS. 1986. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol 137: 323-329.
22. Williams KC, Corey S, Westmoreland SV, Pauley D, Knight H, de Bakker C, Alvarez X, Lackner AA. 2001. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: implications for the neuropathogenesis of AIDS. J Exp Med 193:905-915. http://dx.doi.org/10.1084/jem.193.8.905.
23. Lamers SL, Salemi M, Galligan D, de Oliveira T, Fogel GB, Granier SC, Zhao L, Brown JN, Morris A, Masliah E, McGrath MS. 2009. Extensive HIV-1 intra-host recombination is common in tissues with abnormal histopathology. PLoS One 4:e5065. http://dx.doi.org/10.1371/journal.pone.0005065.
24. Gavegnano C, Detorio MA, Bassit L, Hurwitz SJ, North TW, Schinazi RF. 2013. Cellular pharmacology and potency of HIV-1 nucleoside analogs in primary human macrophages. Antimicrob Agents Chemother 57: 1262-1269. http://dx.doi.org/10.1128/AAC.02012-12.
25. Williams KC, Hickey WF. 2002. Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci 25:537-562. http://dx.doi.org/10.1146/annurev.neuro.25.112701.142822.
26. Gavegnano C, Schinazi RF. 2009. Antiretroviral therapy in macrophages: implication for HIV eradication. Antivir Chem Chemother 20:63-78. http://dx.doi.org/10.3851/IMP1374.
27. Garden GA. 2002. Microglia in human immunodeficiency virus associated neurodegeneration. Glia 40:240-251. http://dx.doi.org/10.1002/glia.10155.
28. Crowe SM, Westhorpe CL, Mukhamedova N, Jaworowski A, Sviridov D, Bukrinsky M. 2010. The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol 87:589-598. http://dx.doi.org/10.1189/jlb.0809580.
29. Gannon P, Khan MZ, Kolson DL. 2011. Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24:275-283. http://dx.doi.org/10.1097/WCO.0b013e32834695fb.
30. Tulpule A, Espina BM, Pedro Santabarbara AB, Palmer M, Schiflett J, Boswell W, Smith S, Levine AM. 2004. Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study. Invest New Drugs 22:63-68. http://dx.doi.org/10.1023/B:DRUG.0000006175.32100.2c.
31. Herr HW, Kleinert EL, Conti PS, Burchenal JH, Whitmore, WF, Jr. 1984. Effects of alpha-difluoromethylornithine and methylglyoxal bis-(guanylhydrazone) on the growth of experimental renal adenocarcinoma in mice. Cancer Res 44:4382-4385.
32. Williams-Ashman HG, Schenone A. 1972. Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast Sadenosylmethionine decarboxylases. Biochem Biophys Res Commun 46: 288-295. http://dx.doi.org/10.1016/0006-291X(72)90661-4.
33. Corti A, Dave C, Williams-Ashman HG, Mihich E, Schenone A. 1974. Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances. Biochem J 139:351-357. http://dx.doi.org/10.1042/bj1390351.
34. Pegg AE. 1973. Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone). Biochem J 132:537-540. http://dx.doi.org/10.1042/bj1320537.
35. Tabor CW, Tabor H. 1976. 1,4-Diaminobutane (putrescine), spermidine, and spermine. Annu Rev Biochem 45:285-306. http://dx.doi.org/10.1146/annurev.bi.45.070176.001441.
36. Pegg AE, McCann PP. 1982. Polyamine metabolism and function. Am J Physiol 243:C212-C221.
37. Jänne J, Hölttä E, Kallio A, Käpyaho K. 1983. Role of polyamines and their antimetabolites in clinical medicine. Spec Top Endocrinol Metab 5:227-293.
38. + monocyte subset is more permissive to infection and preferentially harbors HIV-1 in vivo. J Immunol 178:6581-6589. http://dx.doi.org/10.4049/jimmunol.178.10.6581.
39. + blood monocytes: their role in infection and inflammation. J Leukoc Biol 81:584-592.
40. + peripheral bloodderived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7:528-541. http://dx.doi.org/10.1080/135502801753248114.
41. Messina L, Spampinato G, Arcidiacono A, Malaquarnera L, Paqano M, Kaminska B, Kaczmarek L, Messina A. 1992. Polyamine involvement in functional activation of human macrophages. J Leukoc Biol 52:585-587.
42. Kaczmarek L, Kaminska B, Messina L, Spampinato G, Arcidiacono A, Malaquarnera L, Messina A. 1992. Inhibitors of polyamine biosynthesis block tumor necrosis factor-induced activation of macrophages. Cancer Res 52:1891-1894.
43. Brown A, Islam T, Adams R, Nerle S, Kamara M, Eger C, Marder K, Cohen B, Schifitto G, McArthur JC, Sacktor N, Pardo CA. 2011. Osteopontin enhances HIV replication and is increased in the brain and cerebrospinal fluid of HIV-infected individuals. J Neurovirol 17:382-392. http://dx.doi.org/10.1007/s13365-011-0035-4.
44. Nibbering PH, Zomerdijk TP, Corsel-Van-Tilburg AJ, Van-Furth R. 1990. Mean cell volume of human blood leucocytes and resident and activated murine macrophages. J Immunol Methods 129:143-145. http://dx.doi.org/10.1016/0022-1759(90)90432-U.
45. Chapman EH, Kurec AS, Davey FR. 1981. Cell volumes of normal and malignant mononuclear cells. J Clin Pathol 34:1083-1090. http://dx.doi.org/10.1136/jcp.34.10.1083.
46. Krombach F, Münzing S, Allmeling AM, Gerlach JT, Behr J, Dörger M. 1997. Cell size of alveolar macrophages: an interspecies comparison. Environ Health Perspect 105(Suppl 5):S1261-S1263.
47. GE Healthcare Life Sciences. 2010. Application note 28-9650-52 AC. Perfusion culture of T lymphocytes in the WAVE bioreactor system 2/10 (software version 2.61). GE Healthcare Life Sciences, Pittsburgh, PA.
48. Brown A, Gartner S, Kawano T, Benoit N, Cheng-Mayer C. 2005. HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus. J Leukoc Biol 78:675-685. http://dx.doi.org/10.1189/jlb.0505237.
49. Brown A, Zhang H, Lopez P, Pardo CA, Gartner S. 2006. In vitro modeling of the HIV-macrophage reservoir. J Leukoc Biol 80:1127-1135. http://dx.doi.org/10.1189/jlb.0206126.
50. Koelsch KK, Liu L, Haubrich R, May S, Havlir D, Günthard HF, Ignacio CC, Campos-Soto P, Little SJ, Shafer R, Robbins GK, D'Aquila RT, Kawano Y, Young K, Dao P, Spina CA, Richman DD, Wong JK. 2008. Dynamics of total, linear nonintegrated, and integrated HIV-1DNA in vivo and in vitro. J Infect Dis 197:411-419. http://dx.doi.org/10.1086/525283.
51. Shiramizu B, Ananworanich J, Chalermchai T, Siangphoe U, Troelstrup D, Shikuma C, De Grutolla V, Sithinamsuwan P, Praihirunkit P, Rattanamanee S, Valcour V, SEARCH 001.1 Study Group. 2012. Failure to clear intra-monocyte HIV infection linked to persistent neuropsychological testing impairment after first-line combined antiretroviral therapy. J Neurovirol 18:69-73. http://dx.doi.org/10.1007/s13365-011-0068-8.
52. - cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med 164:280-290. http://dx.doi.org/10.1084/jem.164.1.280.
53. Regenass U, Caravatti G, Mett H, Stanek J, Schneider P, Müller M, Matter A, Vertino P, Porter CW. 1992. New S-adenosylmethionine decarboxylase inhibitors with potent antitumor activity. Cancer Res 52: 4712-4718.
54. Jänne J, Morris DR. 1984. Inhibition of S-adenosylmethionine decarboxylase and diamine oxidase activities by analogues of methylglyoxal bis-(guanylhydrazone) and their cellular uptake during lymphocyte activation. Biochem J 218:947-951. http://dx.doi.org/10.1042/bj2180947.
55. Kakinuma Y, Hoshino K, Igarashi K. 1988. Characterization of the inducible polyamine transporter in bovine lymphocytes. Eur J Biochem 176:409-414. http://dx.doi.org/10.1111/j.1432-1033.1988.tb14297.x.
56. Shimura K, Kodama E, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, Watanabe Y, Ohata Y, Doi S, Sato M, Kano M, Ikeda S, Matsuoka M. 2008. Broad antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137). J Virol 82:764-774. http://dx.doi.org/10.1128/JVI.01534-07.
57. Stoddart CA, Galkina SA, Joshi P, Kosikova G, Long BR, Maidji E, Moreno ME, Rivera JM, Sanford UR, Sloan B, Cieplak W, Wrin T, Chan-Hui PY. 2014. Efficacy of broadly neutralizing monoclonal antibody PG16 in HIV-infected humanized mice. Virology 462-463:115-125. http://dx.doi.org/10.1016/j.virol.2014.05.036.
58. Bergamaschi A, Pancino G. 2010. Host hindrance to HIV-1 replication in monocytes and macrophages. Retrovirology 7:31. http://dx.doi.org/10.1186/1742-4690-7-31.
59. ArfiV, Rivière L, Jarrosson-Wuillème L, Goujon C, Rigal D, Darlix JL, Cimarelli A. 2008. Characterization of the early steps of infection of primary blood monocytes by human immunodeficiency virus type 1. J Virol 82:6557-6565. http://dx.doi.org/10.1128/JVI.02321-07.
60. Ryoo J, Choi J, Oh C, Kim S, Seo M, Kim SY, Seo D, Kim J, White TE, Brandariz-Nuñez A, Diaz-Griffero F, Yun CH, Hollenbaugh JA, Kim B, Baek D, Ahn K. 2014. The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nat Med 20:936-941. http://dx.doi.org/10.1038/nm.3626.
61. Nath A, Schiess N, Venkatesan A, Rumbaugh J, Sacktor N, McArthur J. 2008. Evolution of HIV dementia with HIV infection. Int Rev Psychiatry 20:25-31. http://dx.doi.org/10.1080/09540260701861930.
62. Gras G, Kaul M. 2010. Molecular mechanisms of neuroinvasion by monocytes-macrophages in HIV-1 infection. Retrovirology 7:30. http://dx.doi.org/10.1186/1742-4690-7-30.
63. Subramanian S, Tawakol A, Burdo TH, Abbara S, Wei J, Vijayakumar J, Corsini E, Abdelbaky A, Zanni MV, Hoffmann U, Williams KC, Lo J, Grinspoon SK. 2012. Arterial inflammation in patients with HIV. JAMA 308:379-386. http://dx.doi.org/10.1001/jama.2012.6698.
64. Rudman D, Kutner MH, Chawla RK, Goldsmith MA, Blackston RD, Bain R. 1979. Serum and urine polyamines in normal and in short children. J Clin Invest 64:1661-1668. http://dx.doi.org/10.1172/JCI109628.
65. Shipe JR, Jr, Hunt DF, Savory J. 1979. Plasma polyamines determined by negative-ion chemical ionization/mass spectrometry. Clin Chem 25: 1564-1571.
66. Métifiot M, Marchand C, Maddali K, Pommier Y. 2010. Resistance to integrase inhibitors. Viruses 2:1347-1366. http://dx.doi.org/10.3390/v2071347.
67. Henderson HI, Hope TJ. 2006. The temperature arrested intermediate of virus-cell fusion is a functional step in HIV infection. Virol J 3:36. http://dx.doi.org/10.1186/1743-422X-3-36.
68. Arribas JR, Eron J. 2013. Advances in antiretroviral therapy. Curr Opin HIV AIDS 8:341-349. http://dx.doi.org/10.1097/COH.0b013e328361fabd.
69. Custodio JM, Wang H, Hao J, Lepist EI, Ray AS, Andrews J, Ling KH, Cheng A, Kearney BP, Ramanathan S. 2014. Pharmacokinetics of cobicistat boosted-elvitegravir administered in combination with rosuvastatin. J Clin Pharmacol 54:649-656. http://dx.doi.org/10.1002/jcph.256.
70. Hibasami H, Tsukada T, Maekawa S, Nakashima K. 1986. Antitumor effect of methylglyoxal bis(butylamidinohydrazone), a new inhibitor of S-adenosylmethionine decarboxylase, against human erythroid leukemia K 562 cells. Cancer Lett 30:17-23. http://dx.doi.org/10.1016/0304-3835(86)90127-8.
71. Snyder RD. 1989. Polyamine depletion is associated with altered chromatin structure in HeLa cells. Biochem J 260:697-704. http://dx.doi.org/10.1042/bj2600697.
72. Sartorelli AC, Iannotti AT, Booth BA, Schneider FH, Bertino JR, Johns DG. 1965. Complex formation with DNA and inhibition of nucleic acid synthesis by methylglyoxal bis(guanylhydrazone). Biochim Biophys Acta 103:174-176. http://dx.doi.org/10.1016/0005-2787(65)90550-2.
73. Fesen MR, Kohn KW, Leteurtre F, Pommier Y. 1993. Inhibitors of human immunodeficiency virus integrase. Proc Natl Acad Sci U S A 90: 2399-2403. http://dx.doi.org/10.1073/pnas.90.6.2399.
74. Bakhanashvili M, Rahav G. 2006. The incorporation of nucleoside analogs by human immunodeficiency virus type 1 reverse transcriptase decreases in the presence of polyamines. FEBS Lett 580:5363-5370. http://dx.doi.org/10.1016/j.febslet.2006.08.074.
75. Taltynov O, Desimmie BA, Demeulemeester J, Christ F, Debyser Z. 2012. Cellular cofactors of lentiviral integrase: from target validation to drug discovery. Mol Biol Int 2012:863405. http://dx.doi.org/10.1155/2012/863405.
76. Pesenti E, Pastore C, Lillo F, Siccardi AG, Vercelli D, Lopalco L. 1999. Role of CD4 and CCR5 levels in the susceptibility of primary macrophages to infection by CCR5-dependent HIV type 1 isolates. AIDS Res Hum Retroviruses 15:983-987. http://dx.doi.org/10.1089/088922299310494.
77. Bannert N, Schenten D, Craig S, Sodroski J. 2000. The level of CD4 expression limits infection of primary rhesus monkey macrophages by a T-tropic simian immunodeficiency virus and macrophagetropic human immunodeficiency viruses. J Virol 74:10984-10993. http://dx.doi.org/10.1128/JVI.74.23.10984-10993.2000.
78. Chiang PK, McCann PP, Lane JR, Pankaskie MC, Burke DS, Mayers DL. 1996. Antihuman immunodeficiency virus (HIV-1) activities of inhibitors of polyamine pathways. J Biomed Sci 3:78-81. http://dx.doi.org/10.1007/BF02255534.
79. Schäfer B, Hauber I, Bunk A, Heukeshoven J, Düsedau A, Bevec D, Hauber J. 2006. Inhibition of multidrug-resistant HIV-1 by interference with cellular S-adenosylmethionine decarboxylase activity. J Infect Dis 194:740-750. http://dx.doi.org/10.1086/507043.
80. Lindl KA, Marks DR, Kolson DL, Jordan-Sciutto KL. 2010. HIVassociated neurocognitive disorder: pathogenesis and therapeutic opportunities. J Neuroimmune Pharmacol 5:294-309. http://dx.doi.org/10.1007/s11481-010-9205-z.
81. McGrath M, Jin X, Burdo T, Williams K. 2012. Macrophage targeted therapy for AIDS: regulation of monocyte differentiation with PA300, a novel oral form of MGBG that reverses CNS and myocardial disease in a SIV model, abstr ST106. Annu Int Meet Inst Human Virol. Institute of Human Virology, Baltimore, MD.
82. Burdo T, Blitzer J, McKearn J, Miller A, McGrath M, Williams K. 2012. Treatment of SIV-infected monkeys with a polyamine biosynthesis inhibitor, PA300 that decreases monocyte activation and infection, blocks AIDS and SIV encephalitis. CROI 2012: 19th Conf Retroviruses Opportunistic Infect. CROI, Seattle, WA.
83. Heymann F, Trautwein C, Tacke F. 2009. Monocytes and macrophages as cellular targets in liver fibrosis. Inflamm Allergy Drug Targets 8:307-318. http://dx.doi.org/10.2174/187152809789352230.