A majority of AIDS patients experience HIV-1 infection of the CMS and exhibit neurologic dysfunctions. Astrocytes constitute a major population of cells in the brain, and play an indispensable role in maintaining normal brain functions. HIV-1 infects astrocytes in vitro and in vivo, but in a restricted fashion. HIV-1 infection of astrocytes correlates with clinical dementia of AIDS patients, directly supporting a crucial role of astrocytes in HIV-1-associated neuropathogenesis. It is our long-term objective to identify the molecular mechanisms of HIV pathogenesis in the CMS and thereby develop strategies for treating the neurologic symptoms in AIDS patients and ultimately preventing and eliminating HIV-1 infection in the CNS. The broad goal of this research is to continue our studies of HIV-1 infection and pathogenesis in astrocytes. We have identified the human mannose receptor (hMR) as the CD4-independent HIV-1 receptor for astrocyte infection. In addition, we have also shown that binding of HIV-1 viruses or gp120 protein to hMR in the absence of HIV-1 entry is able to induce matrix metalloproteinase 2 (MMP-2 production through hMR-mediated intracellular signaling. We seek continued support to extend these studies. We have three interrelated specific aims: 1. To characterize molecular determinants of hMR binding to HIV-1 envelope glycoprotein gp120; 2. To determine the relationship between regulation of hMR expression and HIV-1 infection; 3. To determine hMR-mediated signal transduction pathways in astrocytes upon gp120 binding. We will use a variety of biochemical, cellular, and molecular approaches. The answers sought have fundamental significance for understanding of this critical and pervasive population of cells in HIV-1-induced neuronal injury and damage. They should also aid in the development of strategies for treating neurologic symptoms of AIDS patients.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
NeuroAIDS and other End-Organ Diseases Study Section (NAED)
Program Officer
Nunn, Michael
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Indiana University-Purdue University at Indianapolis
Schools of Medicine
United States
Zip Code
Fan, Yan; Timani, Khalid Amine; He, Johnny J (2015) STAT3 and its phosphorylation are involved in HIV-1 Tat-induced transactivation of glial fibrillary acidic protein. Curr HIV Res 13:55-63
Fan, Yan; Zou, Wei; Green, Linden A et al. (2011) Activation of Egr-1 expression in astrocytes by HIV-1 Tat: new insights into astrocyte-mediated Tat neurotoxicity. J Neuroimmune Pharmacol 6:121-9
Zou, Wei; Wang, Zhenyuan; Liu, Ying et al. (2010) Involvement of p300 in constitutive and HIV-1 Tat-activated expression of glial fibrillary acidic protein in astrocytes. Glia 58:1640-8
Henao-Mejia, Jorge; Liu, Ying; Park, In-Woo et al. (2009) Suppression of HIV-1 Nef translation by Sam68 mutant-induced stress granules and nef mRNA sequestration. Mol Cell 33:87-96
He, Johnny J; Henao-Mejia, Jorge; Liu, Ying (2009) Sam68 functions in nuclear export and translation of HIV-1 RNA. RNA Biol 6:384-6
Green, Linden A; Liu, Ying; He, Johnny J (2009) Inhibition of HIV-1 infection and replication by enhancing viral incorporation of innate anti-HIV-1 protein A3G: a non-pathogenic Nef mutant-based anti-HIV strategy. J Biol Chem 284:13363-72
Henao-Mejia, Jorge; He, Johnny J (2009) Sam68 relocalization into stress granules in response to oxidative stress through complexing with TIA-1. Exp Cell Res 315:3381-95
Zou, Wei; Kim, Byung Oh; Zhou, Betty Y et al. (2007) Protection against human immunodeficiency virus type 1 Tat neurotoxicity by Ginkgo biloba extract EGb 761 involving glial fibrillary acidic protein. Am J Pathol 171:1923-35
Lopez-Herrera, Albeiro; Liu, Ying; Rugeles, Maria T et al. (2005) HIV-1 interaction with human mannose receptor (hMR) induces production of matrix metalloproteinase 2 (MMP-2) through hMR-mediated intracellular signaling in astrocytes. Biochim Biophys Acta 1741:55-64
Zhang, Jizhong; Li, Geling; Bafica, Andre et al. (2005) Neisseria gonorrhoeae enhances infection of dendritic cells by HIV type 1. J Immunol 174:7995-8002

Showing the most recent 10 out of 20 publications