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"Role of Pannexin1 Channels in the Pathogenesis of HIV and Multiple Sclerosis"

by
Stephani Velasquez
Infection, Immunity and Inflammation, Ph.D. Program
B.S. 2011, Kean University, Union, NJ


Thesis Advisor: Eliseo Eugenin, Ph.D.
Associate Professor
Department of Microbiology, Biochemistry and Molecular Genetics

Wednesday, December 2, 2015
10:00 A.M., ICPH 1st floor auditorium


Abstract

Pannexin1 (Panx1) channels are large high conductance channels found in all vertebrates and normally are in a close state. During my thesis I demonstrated that HIV results in the extended opening of Panx1 channels (5 min - 60 min), allowing for the secretion of ATP through the channel with subsequent activation of purinergic receptors, which facilitates HIV entry and replication. In addition, I identified that chemokines, which bind CCR5 and CXCR4, especially SDF-1α/CXCL12, result in a transient opening (5 min) of Panx1 channels, ATP secretion, focal adhesion kinase phosphorylation and subsequent migration. Blocking the channel abolished HIV entry and replication as well as migration in response to chemokines. Our data in vivo, using samples obtained from uninfected and HIV infected individuals demonstrated that ethnicities with increased susceptibility to HIV infection such as African Americans, and Hispanics had higher expression of Panx1 mRNA and protein when compared to Caucasians. In addition, HIV infected individuals show spontaneous opening of the Panx1 channels in PBMCs resulting in the constant release of intracellular inflammatory factors such as ATP and PGE2 through the channel pore ensuing systemic inflammation. We propose that Panx1 channel is a potential target for the development of therapies, which could reduce the devastating consequences of HIV and Multiple Sclerosis.


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