Authors: Mahajan, Supriya D.; Aalinkeel, Ravikumar; Reynolds, Jessica L.; Nair, Bindukumar B.; Fernandez, Stanley F.; Schwartz, Stanley A.; Nair, Madhavan P.N.

Source: Current HIV Research, Volume 3, Number 3, July 2005 , pp. 277-288(12)

Publisher: Bentham Science Publishers

Abstract:

HIV-1 affects microglia and astroglia, which subsequently contributes to the neurodegenerative changes. Viral proteins cause neurotoxicity by direct action on the CNS cells or by activating glial cells to cause the release of cytokines, chemokines or neurotoxic substances. Opioid abuse has been postulated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) infection and AIDS. HIV-induced pathogenesis is exacerbated by opiate abuse and that the synergistic neurotoxicity is a direct effect of opiates on the CNS. Chemokines and their receptors have been implicated in the pathogenesis of neuroAIDS. Herein we describe the effects of morphine and/or gp120 on the expression of the genes for the chemokine MIP-1 and its receptors CCR3 and CCR5 by the U373 cells which are a human brain-derived astrocytoma/glioblastoma cell line. Our results indicate that treatment of U373 cells with morphine significantly downregulated the gene expression of the chemokine, MIP1 , while reciprocally upregulating the expression of its specific receptors, CCR3 and CCR5 suggesting that the capacity of mu-opioids to increase HIV-1 co-receptor expression may promote viral binding, trafficking of HIV-1-infected cells, and enhanced disease progression. Additionally, opiates can enhance the cytotoxicity of HIV-1 viral protein gp120 via mechanisms that involve intracellular calcium modulation resulting in direct actions on astroglia, making them an important cellular target for HIV-opiate interactions.

Keywords: morphine; astroglia; hiv; gp; chemokines

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1570162054368048

Affiliations: 1: Department of Medicine, Div of Allergy, Immunology, and Rheumatology, 301 Multi Research Bldg., Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, USA.

Publication date: 2005-07-01

More about this publication?

• Current HIV Research aims to cover all the latest and outstanding developments of HIV research. We invite comprehensive review articles and novel, pioneering work in the basic and clinical fields on all areas of HIV research, including virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Each issue of the journal contains a series of timely in-depth reviews and original research written by leaders in the field covering a range of current topics on HIV research. Periodically, the journal will invite guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.

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