Modeling the Effects of Morphine on Simian Immunodeficiency Virus Dynamics.
Complications of HIV-1 infection in individuals who utilize drugs of abuse is a significant problem, because these drugs have been associated with higher virus replication and accelerated disease progression as well as severe neuropathogenesis. To gain further insight it is important to quantify the effects of drugs of abuse on HIV-1 infection dynamics. Here, we develop a mathematical model that incorporates experimentally observed effects of morphine on inducing HIV-1 co-receptor expression. For comparison we also considered viral dynamic models with cytolytic or noncytolytic effector cell responses. Based on the small sample size Akaike information criterion, these models were inferior to the new model based on changes in co-receptor expression. The model with morphine affecting co-receptor expression agrees well with the experimental data from simian immunodeficiency virus infections in morphine-addicted macaques. Our results show that morphine promotes a target cell subpopulation switch from a lower level of susceptibility to a state that is about 2-orders of magnitude higher in susceptibility to SIV infection. As a result, the proportion of target cells with higher susceptibility remains extremely high in morphine conditioning. Such a morphine-induced population switch not only has adverse effects on the replication rate, but also results in a higher steady state viral load and larger CD4 count drops. Moreover, morphine conditioning may pose extra obstacles to controlling viral load during antiretroviral therapy, such as pre-exposure prophylaxis and post infection treatments. This study provides, for the first time, a viral dynamics model, viral dynamics parameters, and related analytical and simulation results for SIV dynamics under drugs of abuse.
Department of Mathematics and Statistics, University of Missouri-Kansas City, Missouri, United States of America.|Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, Missouri, United States of America.
Naveen K
NK
Vaidya
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Ruy M
RM
Ribeiro
Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, New Mexico, United States of America.
Alan S
AS
Perelson
Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, Missouri, United States of America.
Anil
A
Kumar
J Investig Med. 2002 Nov;50(6):435-42
12425430
J Neuroimmunol. 2013 Dec 15;265(1-2):43-50
24090653
Adv Biochem Psychopharmacol. 1988;44:145-58
3041744
PLoS Comput Biol. 2011 Sep;7(9):e1002200
21990968
Virology. 2006 Oct 10;354(1):192-206
16876224
N Engl J Med. 1992 Dec 10;327(24):1697-703
1359411
J Virol. 2002 May;76(10):5271-3
11967341
Lancet. 1999 Nov 20;354(9192):1782-5
10577640
J Virol. 2010 May;84(9):4302-10
20147390
Clin Immunol. 2005 Jun;115(3):323-32
15893700
Cell. 2002 Jul 26;110(2):135-8
12150921
J Acquir Immune Defic Syndr. 2009 Mar 1;50(3):241-9
19194320
J Virol. 2008 Dec;82(24):12449-63
18842730
Cytokine Growth Factor Rev. 2001 Jun-Sep;12(2-3):219-43
11325604
J Biol Chem. 2000 Oct 6;275(40):31305-10
10887175
BMC Biol. 2013 Sep 03;11:96
24020860
Neurology. 2007 Oct 30;69(18):1789-99
17914061
J Theor Biol. 2000 Apr 7;203(3):285-301
10716909
J Neuroimmune Pharmacol. 2008 Dec;3(4):275-85
18815890
J Neuroimmunol. 1998 Mar 15;83(1-2):77-87
9610676
Virology. 2003 Apr 25;309(1):99-107
12726730
J Virol. 2009 Apr;83(7):3288-97
19129448
PLoS Comput Biol. 2010 Aug 26;6(8):
20865048
J Neuroimmune Pharmacol. 2010 Mar;5(1):122-32
20013315
J Infect Dis. 2002 Jun 15;185(12):1826-9
12085334
Brain. 1998 Nov;121 ( Pt 11):2043-52
9827765
Science. 1999 Feb 5;283(5403):857-60
9933172
Clin Infect Dis. 2005 Oct 1;41(7):1027-34
16142670
J Exp Med. 1998 Apr 20;187(8):1295-303
9547340
AIDS Res Hum Retroviruses. 2006 Jan;22(1):114-9
16438654
J Virol. 1997 Oct;71(10):7518-25
9311831
J Infect Dis. 2003 Mar 15;187(6):896-900
12660935
J Exp Med. 1999 Sep 20;190(6):841-50
10499922
Science. 1996 Jan 26;271(5248):497-9
8560262
Pediatr Res. 2003 Aug;54(2):282-8
12736382
J Neurovirol. 2009 May;15(3):219-28
19462331
J Neuroimmunol. 2000 Oct 2;110(1-2):230-9
11024554
AIDS Res Hum Retroviruses. 2010 Aug;26(8):919-22
20672973
Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19079-84
18025463
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6971-6
9192676
Clin Infect Dis. 1995 Jun;20(6):1467-79
7548494
Nat Rev Immunol. 2002 Jan;2(1):28-36
11905835
J Theor Biol. 2009 Aug 21;259(4):751-9
19389409
Top HIV Med. 2003 Jan-Feb;11(1):20-4
12717047
J Virol. 2010 Jun;84(12):6096-102
20357090
J Virol. 2003 Apr;77(8):5037-8
12663814
J Exp Med. 1997 May 5;185(9):1681-91
9151905
AIDS Res Treat. 2012;2012:953678
22666564
J Virol. 2004 May;78(9):4866-75
15078967
J Neurovirol. 2001 Feb;7(1):66-71
11519485
PLoS One. 2012;7(2):e31167
22359571
J Virol. 2004 Oct;78(20):11425-8
15452267
AIDS. 2000 Jan 7;14(1):75-83
10714570
PLoS Pathog. 2012;8(5):e1002721
22693447
Trends Immunol. 2002 Jul;23(7):347-51
12103354
Am J Pathol. 1996 Nov;149(5):1459-67
8909235
Curr HIV Res. 2006 Jul;4(3):249-57
16842078