Abstract

Approximately 30 percent of HIV-positive patients have a history of injection drug abuse that frequently involves the use of opiates. Because of the substantial evidence that both endogenous and exogenous opioids and opiate-abuse modulate immune function, and also that opiates augment HIV-1 replication in vitro, there continues to be a extended debate and considerable research has been aimed at understanding whether opiates alter HIV-1 infection and progression to AIDS. The present application is designed to address this important question in SHIV KU- 2/macaque model of AIDS. This model of HIV/AIDS has been successfully used in our laboratory to study the pathogenesis of the virus, effect of anti retroviral drugs and evaluation of different candidate vaccines. We will use morphine sulfate to establish opiate-dependence in macaques by intramuscular injection, and infect these macaques along with control animals with highly pathogenic SHIV KU-2. These experiments will determine, whether morphine treatment alters the expression of mu-opioid receptor (MOR) in monkeys, and whether morphine- dependence enhances intensity of SHIV KU-2 replication in vivo and accelerates the onset of clinical disease in SHIV/macaque model of HIV/AIDS. We will also examine the effect of morphine treatment on in vivo apoptosis of T cells. In another series of experiments we will examine the effect of morphine addiction on the development and persistence of virus-specific immune responses that will help us understand effect of drug-abuse on the development of immune responses, induced by a vaccine. We will immunize morphine-dependent and control macaques with a live virus vaccine that has been shown to confer solid protection against SHIV-induced AIDS. The virus-specific immune response in these two groups will be compared for the strength and duration. These animals will be challenged with pathogenic SHIV KU-2 to determine whether morphine-dependence compromises the live vaccine-induced protection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA015013-03
Application #
6515963
Study Section
AIDS and Related Research 8 (AARR)
Program Officer
Sharp, Charles
Project Start
2001-09-19
Project End
2005-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
3
Fiscal Year
2003
Total Cost
$236,262
Indirect Cost

  Institution

Name
Ponce School of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
105742043
City
Ponce
State
PR
Country
United States
Zip Code
00732

  Publications

Rivera, Ivelisse; García, Yashira; Gangwani, Mohitkumar R et al. (2013) Identification and molecular characterization of SIV Vpr R50G mutation associated with long term survival in SIV-infected morphine dependent and control macaques. Virology 446:144-51
Silverstein, Peter S; Shah, Ankit; Weemhoff, James et al. (2012) HIV-1 gp120 and drugs of abuse: interactions in the central nervous system. Curr HIV Res 10:369-83
Chaudhary, Suman; Noel, Richard J; Rodriguez, Nayra et al. (2011) Correlation between CD4 T cell counts and virus compartmentalization in genital and systemic compartments of HIV-infected females. Virology 417:320-6
Silverstein, Peter S; Audus, Kenneth L; Qureshi, Nilofer et al. (2010) Lipopolysaccharide increases the expression of multidrug resistance-associated protein 1 (MRP1) in RAW 264.7 macrophages. J Neuroimmune Pharmacol 5:516-20
Rivera-Amill, Vanessa; Kumar, Rakesh; Noel Jr, Richard J et al. (2010) Short communication: Lack of immune response in rapid progressor morphine-dependent and SIV/SHIV-infected rhesus macaques is correlated with downregulation of TH1 cytokines. AIDS Res Hum Retroviruses 26:919-22
Rivera-Amill, Vanessa; Noel Jr, Richard J; Garcia, Yashira et al. (2010) Accelerated evolution of SIV env within the cerebral compartment in the setting of morphine-dependent rapid disease progression. Virology 398:201-7
Rivera-Amill, Vanessa; Silverstein, Peter S; Noel Jr, Richard J et al. (2010) Morphine and rapid disease progression in nonhuman primate model of AIDS: inverse correlation between disease progression and virus evolution. J Neuroimmune Pharmacol 5:122-32
Rivera-Amill, Vanessa; Noel Jr, Richard J; Román, Ivelisse Rivera et al. (2009) Analysis of the V1V2 region of the SIV envelope in the brains of morphine-dependent and control SIV/SHIV-infected macaques. AIDS Res Hum Retroviruses 25:531-4
Kumar, Anil; Liu, Zhenqian; Sheffer, Darlene et al. (2008) Protection of macaques against AIDS with a live attenuated SHIV vaccine is of finite duration. Virology 371:238-45
Noel Jr, Richard J; Rivera-Amill, Vanessa; Buch, Shilpa et al. (2008) Opiates, immune system, acquired immunodeficiency syndrome, and nonhuman primate model. J Neurovirol 14:279-85

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