“Morphine-dependency and SIV/SHIV Disease
Progression in the Macaque Model of AIDS”

Biographical Sketch

Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS in the United States and other countries. However, conflicting reports in human studies claiming both survival advantage and disadvantage have been described in the setting of drug abuse. We developed the non-human morphine-dependent primate model of HIV/AIDS in Indian rhesus macaques in order to circumvent major issues in human studies. In this model we use a mixture of three viruses that lead to massive CD4+ T cell loss and neurological disorders mimicking what happens in the human host. Studies demonstrated that the morphine-dependent animals exhibited higher viral loads. In addition, a fraction of the morphine-dependent macaques developed an accelerated form of SIV/SHIV induced disease and died within 20 weeks.

Based on these observations we hypothesize that morphine may exacerbate SIV/SHIV infection and contribute to the early onset of the disease. We also hypothesize that morphine may potentiate viral evolution. The present application is designed to address these vital questions in our SIV/SHIV macaque model of AIDS. This model of HIV/AIDS has been successfully used in our laboratory to study viral pathogenesis. The experiments in this proposal are designed to further expand our work in the characterization of morphine contribution to SIV/SHIV evolution and disease progression. In specific aims 1 and 2 we will compare pre-infection and post-infection samples in the morphine-dependent vs. control macaques in terms of humoral and cellular responses. This will be followed by specific aim 3 in which we will determine the differential viral migration and distribution. Finally, in specific aim 4 we will focus on the sequence analysis of the envelope and tat genes of SIV in various tissue compartments.

These studies will not only help us to better understand the accelerated form of the disease, viral evolution and distribution, but may also refine the development of vaccines and antivirals.