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"My research is aimed on understanding how HIV-1 crosses the BBB and enters the brain. The molecular mechanisms of HIV-1 entry into the CNS remain enigmatic. A major possibility is via direct infection of brain microvascular endothelial cells (BMVECs), which along with astrocytes represent the major constituent of the BBB. Given that these cells lack CD4, the primary cellular receptor for HIV-1 had been a major mystery. We have recently reported that cell-associated proteoglycans (PGs) act as the primary entry receptors for HIV-1 on BMVECs. Our most recent data also indicate that PGs are implicated in viral attachment and entry into brain astrocytes. It's also shown that unspecified PGs interact with HIV-1 Tat and gp120, and we recently identified that perlecan, a specific PG-class, mediates cellular uptake of Tat through a pathway responsible for biological activity. Our central hypothesis is that distinct cell-associated PGs play differential role(s) in viral capture and entry into BMVECs and astrocytes. In addition, PGs may be required for interactions of viral proteins (i.e.HIV-1 Tat, and gp120) with the BBB and CNS-derived cells. Our main objective is to identify the molecular mechanisms of HIV-1 entry and infection of the CNS focusing on PG-species as the primary attachment receptors, and their interactions with certain HIV-1 proteins.
In our laboratory, we use a variety of complementary approaches, including tissue culture (primary and cell lines), molecular biology (RT-PCR, microarrays, gene cloning, transfection), molecular virology assays, cell-biology and protein analysis, biochemical, enzymatic and RNAi.
We hope that our studies will provide new insights into the role of distinct CNS-PGs in HIV-1 infection of the brain, as well as into the interactions of proteoglycans with specific HIV-1 proteins and will help develop new strategies for the treatment of HIV-1 infection and AIDS-associated neuronal disorders."
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- Ph.D., 1991, Sofia University St. Kliment Ohridski - Medical University of Sofia, Bulgaria (Molecular Genetics)
- Post-Doctoral Fellow, 1993-2001, University of Pennsylvania, Philadelphia, PA (ImmunoGenetics / Microbiology)
- Research Associate, 2001-2007, Thomas Jefferson University, Philadelphia, PA (Molecular Virology / NeuroVirology)
Neurodegenerative Diseases, NeuroAIDS, HIV-1-Associated Dementia, AIDS, HIV-1
Click here to view publications of this faculty member
Phone: 215-503-1257
Fax: 215-923-1956
Elias.Argyris@jefferson.edu
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