title: HIV-associated neuropathogenesis: a systems biology perspective for modeling and therapy.
abstract: Despite the development of powerful antiretroviral drugs, HIV-1 associated neurological disorders (HAND) will affect approximately half of those infected with HIV-1. Combined anti-retroviral therapy (cART) targets viral replication and increases T-cell counts, but it does not always control macrophage polarization, brain infection or inflammation. Moreover, it remains difficult to identify those at risk for HAND. New therapies that focus on modulating host immune response by making use of biological pathways could prove to be more effective than cART for the treatment of neuroAIDS. Additionally, while numerous HAND biomarkers have been suggested, they are of little use without methods for appropriate data integration and a systems-level interpretation. Machine learning, could be used to develop multifactorial computational models that provide clinicians and researchers with the ability to identify which factors (in what combination and relative importance) are considered important to outcome.
authors.affiliation: Bioinfoexperts, LLC, PO Box 693, Thibodaux, LA 70301, USA. Electronic address: susanna@bioinfox.com.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lamers
authors.affiliation: Natural Selection, Inc., 5910 Pacific Center Blvd Suite 315, San Diego, CA 92121, USA. Electronic address: gfogel@natural-selection.com.
authors.forename: Gary B
authors.initials: GB
authors.lastname: Fogel
authors.affiliation: University of Florida, 2055 Mowry Road, Department of Pathology and Laboratory Medicine, Gainesville, FL 32610, USA. Electronic address: djnolan@ufl.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nolan
authors.affiliation: University of California, 1001 Potrero Avenue, Building 20, 4(th) Floor, Room 2407, San Francisco, CA 94110-3518, USA. Electronic address: mmcgrath@hemeonc.ucsf.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: McGrath
authors.affiliation: University of Florida, 2055 Mowry Road, Department of Pathology and Laboratory Medicine, Gainesville, FL 32610, USA. Electronic address: salemi@pathology.ufl.edu.
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
mesh_terms: D001185:Artificial Intelligence; D001921:Brain / Q000473:pathology* / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological; D009422:Nervous System Diseases / Q000209:etiology / Q000473:pathology* / Q000628:therapy / Q000821:virology; D049490:Systems Biology / Q000379:methods*
keywords: Brain; Data integration; HIV; Machine learning; Macrophages; Microglia; Neuropathogenesis; microRNA
references.citation: J Biol Chem. 2011 May 27;286(21):19047-64
references.pmid: 21471217
references.citation: Curr HIV Res. 2010 Dec;8(8):638-40
references.pmid: 21067513
references.citation: Immunol Rev. 2013 Jul;254(1):102-13
references.pmid: 23772617
references.citation: PLoS One. 2013 Jul 03;8(7):e67672
references.pmid: 23844055
references.citation: J Biol Chem. 2011 Nov 25;286(47):41125-34
references.pmid: 21956116
references.citation: AIDS. 2011 Mar 13;25(5):577-80
references.pmid: 21160414
references.citation: PLoS One. 2011 Feb 09;6(2):e16659
references.pmid: 21347424
references.citation: J Infect Dis. 1999 Apr;179(4):832-42
references.pmid: 10068578
references.citation: EMBO J. 2011 Nov 25;30(24):4998-5009
references.pmid: 22117217
references.citation: Sci China C Life Sci. 2009 Jul;52(7):651-6
references.pmid: 19641870
references.citation: J Neurovirol. 1999 Oct;5(5):519-28
references.pmid: 10568889
references.citation: J Immunol. 2007 Jun 15;178(12):7658-66
references.pmid: 17548602
references.citation: J Neuroimmune Pharmacol. 2013 Mar;8(1):118-31
references.pmid: 22527632
references.citation: J Virol. 2007 Sep;81(17):9078-87
references.pmid: 17581988
references.citation: PLoS Biol. 2004 Nov;2(11):e363
references.pmid: 15502875
references.citation: PLoS One. 2012;7(9):e46178
references.pmid: 23049970
references.citation: Brain Res. 2007 Feb 2;1131(1):37-43
references.pmid: 17182009
references.citation: Annu Rev Neurosci. 2002;25:537-62
references.pmid: 12052920
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D222-9
references.pmid: 22135297
references.citation: J Genet Genomics. 2009 Jul;36(7):409-16
references.pmid: 19631915
references.citation: J Neurovirol. 2001 Dec;7(6):528-41
references.pmid: 11704885
references.citation: J Cell Sci. 2006 Nov 1;119(Pt 21):4520-30
references.pmid: 17046994
references.citation: J Biol Chem. 2007 Sep 14;282(37):26641-26645
references.pmid: 17627941
references.citation: BMC Neurosci. 2008 Feb 26;9:27
references.pmid: 18302767
references.citation: Neurology. 2007 Oct 30;69(18):1789-99
references.pmid: 17914061
references.citation: Ann Neurol. 1986 Jun;19(6):517-24
references.pmid: 3729308
references.citation: PLoS One. 2010 Apr 26;5(4):e10337
references.pmid: 20436668
references.citation: Ann Neurol. 1983 Oct;14(4):403-18
references.pmid: 6314874
references.citation: Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1445-52
references.pmid: 22516068
references.citation: Acta Pathol Jpn. 1991 Mar;41(3):182-91
references.pmid: 2068942
references.citation: Genes Dev. 2006 May 1;20(9):1123-36
references.pmid: 16618801
references.citation: J Virol. 2003 Jun;77(12):6855-66
references.pmid: 12768005
references.citation: J Intern Med. 2008 Jan;263(1):28-42
references.pmid: 18042221
references.citation: Nat Rev Immunol. 2008 Dec;8(12):958-69
references.pmid: 19029990
references.citation: Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9093-8
references.pmid: 18577589
references.citation: J Neurosci. 2011 Jun 29;31(26):9456-65
references.pmid: 21715610
references.citation: Antioxid Redox Signal. 2013 Aug 20;19(6):595-637
references.pmid: 23311665
references.citation: Glia. 2013 Jan;61(1):91-103
references.pmid: 22653784
references.citation: Nat Rev Microbiol. 2011 Oct 17;9(12):860-75
references.pmid: 22002165
references.citation: Semin Cancer Biol. 2008 Oct;18(5):349-55
references.pmid: 18467122
references.citation: Hum Immunol. 2009 May;70(5):325-30
references.pmid: 19236898
references.citation: J Natl Cancer Inst Monogr. 2011;2011(42):1-7
references.pmid: 21672889
references.citation: J Virol. 1995 Apr;69(4):2159-67
references.pmid: 7884864
references.citation: Int J STD AIDS. 2011 Oct;22(10):608-9
references.pmid: 21998185
references.citation: Ann Intern Med. 1987 Dec;107(6):828-36
references.pmid: 3688675
references.citation: Ann Neurol. 2008 Feb;63(2):213-21
references.pmid: 17894380
references.citation: J Acquir Immune Defic Syndr. 2012 Jul 1;60(3):234-43
references.pmid: 22569268
references.citation: Glia. 2002 Nov;40(2):240-51
references.pmid: 12379911
references.citation: Lab Invest. 2011 Oct;91(10):1472-9
references.pmid: 21709669
references.citation: Biochem Biophys Res Commun. 2013 May 3;434(2):228-34
references.pmid: 23535375
references.citation: Pharmacol Ther. 2012 Feb;133(2):142-50
references.pmid: 22008259
references.citation: Acta Neuropathol. 1987;75(2):185-98
references.pmid: 3434225
references.citation: Am J Physiol Heart Circ Physiol. 2010 Sep;299(3):H656-63
references.pmid: 20622108
references.citation: J Infect Dis. 2010 Jul 1;202(1):125-35
references.pmid: 20486857
references.citation: Int Rev Immunol. 2012 Dec;31(6):432-50
references.pmid: 23215766
references.citation: Crit Rev Clin Lab Sci. 2012 Mar-Apr;49(2):49-61
references.pmid: 22468857
references.citation: J Proteome Res. 2014 Apr 4;13(4):2109-19
references.pmid: 24564501
references.citation: Glia. 2001 Nov;36(2):156-64
references.pmid: 11596124
references.citation: Cell Death Dis. 2010;1:e77
references.pmid: 21170291
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Feb;21(2):253-5
references.pmid: 22313938
references.citation: Blood. 2008 Nov 15;112(10):4202-12
references.pmid: 18713946
references.citation: J Leukoc Biol. 2010 Apr;87(4):599-608
references.pmid: 20042468
references.citation: PLoS One. 2011;6(8):e23892
references.pmid: 21901143
references.citation: Blood. 2011 May 12;117(19):5092-101
references.pmid: 21389328
references.citation: Infect Agent Cancer. 2007 Mar 02;2:7
references.pmid: 17335575
references.citation: Science. 2007 Aug 31;317(5842):1220-4
references.pmid: 17761882
references.citation: Brain Pathol. 1991 Apr;1(3):143-52
references.pmid: 1669703
references.citation: AIDS. 2011 Mar 13;25(5):625-33
references.pmid: 21297425
references.citation: Neurology. 2010 Dec 7;75(23):2087-96
references.pmid: 21135382
references.citation: J Neurovirol. 2009 Sep;15(5-6):360-70
references.pmid: 20175693
references.citation: Nature. 2005 Jun 9;435(7043):834-8
references.pmid: 15944708
references.citation: Rev Neurol (Paris). 1998 Dec;154(12):816-29
references.pmid: 9932303
references.citation: J Virol. 2005 Sep;79(17):11343-52
references.pmid: 16103186
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: J Neurovirol. 1996 Jun;2(3):158-66
references.pmid: 8799208
references.citation: J Neurosci Res. 2005 Aug 1;81(3):374-89
references.pmid: 15959904
references.citation: Int J Biochem Cell Biol. 2012 Jun;44(6):838-41
references.pmid: 22484430
references.citation: J Virol. 2000 Jun;74(11):5040-52
references.pmid: 10799578
references.citation: IEEE/ACM Trans Comput Biol Bioinform. 2008 Apr-Jun;5(2):291-300
references.pmid: 18451438
references.citation: Int J Cell Biol. 2012;2012:501962
references.pmid: 22505929
references.citation: Toxicol Lett. 2012 Feb 25;209(1):94-105
references.pmid: 22178568
references.citation: Front Biosci (Landmark Ed). 2011 Jun 01;16:2187-205
references.pmid: 21622170
references.citation: Ann Neurol. 1995 Nov;38(5):755-62
references.pmid: 7486867
references.citation: Arch Neurol. 2004 Nov;61(11):1687-96
references.pmid: 15534180
references.citation: J Neurovirol. 2009 May;15(3):238-48
references.pmid: 19455469
references.citation: Virology. 2004 Nov 24;329(2):302-18
references.pmid: 15518810
references.citation: J Immunol. 2008 Jun 15;180(12):7878-86
references.pmid: 18523251
references.citation: J Endotoxin Res. 2006;12(5):278-84
references.pmid: 17059691
references.citation: Biochim Biophys Acta. 2011 Nov-Dec;1809(11-12):686-93
references.pmid: 21640212
references.citation: Neuropathol Appl Neurobiol. 2007 Dec;33(6):644-57
references.pmid: 17573813
references.citation: Transpl Immunol. 2008 Apr;19(1):81-5
references.pmid: 18346642
references.citation: Ann Neurol. 1987 May;21(5):490-6
references.pmid: 3296948
references.citation: PLoS One. 2009 Dec 03;4(12):e8153
references.pmid: 19997510
references.citation: J Virol. 2011 Dec;85(23):12614-21
references.pmid: 21937648
references.citation: J Immunol. 1999 Aug 1;163(3):1237-45
references.pmid: 10415019
references.citation: J Neurovirol. 2010 May;16(3):230-41
references.pmid: 20367240
references.citation: Eur J Neurosci. 2006 Feb;23(4):957-64
references.pmid: 16519660
references.citation: Ann Neurol. 1990 Oct;28(4):556-60
references.pmid: 2252366
references.citation: Neurology. 2002 Nov 26;59(10):1563-7
references.pmid: 12451198
references.citation: J Cereb Blood Flow Metab. 2010 Sep;30(9):1564-76
references.pmid: 20606686
references.citation: J Neuroimmune Pharmacol. 2010 Dec;5(4):489-95
references.pmid: 20354805
references.citation: Neurology. 1992 Sep;42(9):1736-9
references.pmid: 1513462
references.citation: Neurodegener Dis. 2012;10(1-4):116-21
references.pmid: 22398391
references.citation: Arch Neurol. 2008 Jan;65(1):65-70
references.pmid: 18195140
references.citation: Nature. 2011 Apr 28;472(7344):495-8
references.pmid: 21499264
references.citation: J Cell Biochem. 1998 Oct 1;71(1):36-45
references.pmid: 9736452
references.citation: Arterioscler Thromb Vasc Biol. 2011 Jun;31(6):1397-402
references.pmid: 21415385
references.citation: PLoS One. 2009;4(3):e5065
references.pmid: 19333384
references.citation: J Neurol. 2003 Aug;250(8):901-6
references.pmid: 12928906
references.citation: J Neurovirol. 2001 Feb;7(1):56-60
references.pmid: 11519483
references.citation: J Neuroimmune Pharmacol. 2012 Jun;7(2):363-71
references.pmid: 22167311
references.citation: Retrovirology. 2010 Apr 09;7:33
references.pmid: 20380696
references.citation: Immunopharmacol Immunotoxicol. 2010 Jun;32(2):181-95
references.pmid: 20170421
references.citation: Viruses. 2011 Jul;3(7):1166-78
references.pmid: 21994775
references.citation: Neurotherapeutics. 2010 Oct;7(4):392-8
references.pmid: 20880503
references.citation: J Neuroimmune Pharmacol. 2007 Mar;2(1):8-13
references.pmid: 18040820
references.citation: J Exp Med. 2008 Mar 17;205(3):585-94
references.pmid: 18299402
references.citation: Ann Neurol. 1997 Dec;42(6):963-72
references.pmid: 9403489
references.citation: Neurology. 1993 Sep;43(9):1813-7
references.pmid: 8414037