Elias Argyris, PhD

Contact Dr. Argyris

900 Walnut St.

Philadelphia, PA 19107

(215) 503-1257
(215) 923-1956 fax

How Does HIV-1 Cross the Blood-Brain Barrier (BBB) and How Dies it Infect and Damage the Brain?

"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."

Publications

Most recent Peer-reviewed Publications

1. The interferon-induced expression of APOBEC3G in human blood-brain barrier exerts a potent intrinsic immunity to block HIV-1 entry to central nervous system
2. Cellular microRNAs contribute to HIV-1 latency in resting primary CD4 + T lymphocytes
3. Analysis of the CD2 and spliceosomal Sm B/B′ polyproline-arginine motifs defined by a monoclonal antibody using a phage-displayed random peptide library
4. Inhibition of endogenous reverse transcription of human and nonhuman primate lentiviruses: Potential for development of lentivirucides
5. Inhibition of HIV-1 replication by caffeine and caffeine-related methylxanthines
6. Caffeine inhibits human immunodeficiency virus type 1 transduction of nondividing cells
7. IL-7 is a potent and proviral strain-specific inducer of latent HIV-1 cellular reservoirs of infected individuals on virally suppressive HAART
8. The perlecan heparan sulfate proteoglycan mediates cellular uptake of HIV-1 Tat through a pathway responsible for biological activity
9. HIV-1 Vif versus APOBEC3G: Newly appreciated warriors in the ancient battle between virus and host
10. The N-terminal domain of APJ, a CNS-based coreceptor for HIV-1, is essential for its receptor function and coreceptor activity
11. Human Immunodeficiency Virus Type 1 Enters Primary Human Brain Microvascular Endothelial Cells by a Mechanism Involving Cell Surface Proteoglycans Independent of Lipid Rafts
12. Human leukocyte antigen Class II amino acid epitopes susceptibility and progression markers for beryllium hypersensitivity
13. Mutagenesis of key residues identifies the connection subdomain of HIV-1 reverse transcriptase as the site of inhibition by heme
14. The connection domain is implicated in metalloporphyrin binding and inhibition of HIV reverse transcriptase
15. Identification of DRB1 allele (DRB1*1316) with aspartate at position 86: Evolutionary considerations and functional implications
16. Genetic markers in beryllium hypersensitivity
17. New DRB1(*)1120 allele; another example of the transition between the DR11 and DR13 families of alleles
18. Structural basis for major histocompatibility complex (MHC)-linked susceptibility to autoimmunity: Charged residues of a single MHC binding pocket confer selective presentation of self-peptides in pemphigus vulgaris
19. Employment of random peptide libraries for the identification of peptide motifs and peptides bound to diabetogenic HLA-DQ molecules
20. Identification of HLA-DRB1*1114 by oligonucleotide typing and DNA sequencing

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