Edward B. Stephens, PhD

Professional Background

I have worked on retroviruses and specifically lentiviruses since 1990. During this period, I have worked on both the simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infections of macaques as models of HIV-1 disease. I was part of the team that first adapted the SHIV to cause CD4+ T cell
depletion and disease in pig-tailed and rhesus macaques and developed the SHIV/macaque model to examine the role of Vpu of SHIV in virus pathogenesis. Other accomplishments with the SHIV model include the first to show that Vpu was required for SHIV to cause disease in macaques, that the casein kinase II sites and
transmembrane domains of Vpu were required for SHIV-mediated CD4+ T cell loss in macaques. My laboratory showed that CD4 down-regulation was a conserved function of Vpu proteins from SIVcpz strains. Along with Dr. Guatelli’s group, we were the second group to show that Vpu down-regulates the BST-2 protein
and that Vpu antagonizes BST-2-mediated restriction of HIV-1 release via â-TrCP and endo-lysosomal trafficking. My laboratory has also published on the requirements of the membrane proximal and dileucine motifs in the transport of the subtype C Vpu proteins and identified amino acids within the second alpha-helical domain that were important for preventing CD4 surface expression. My laboratory has worked with Dr. Kalamvoki for the last three years analyzing HSV-1 proteins for the ability to restrict the release of infectious HIV-1 from cells, which has resulted in two publications and another under review. Thus, we have extensive experience with working on the Vpu protein and other viral membrane proteins, have an extensive collection of BST-2 mutants site-directed mutants, are well versed in cell biology and immunofluorescence techniques and various aspects of molecular cell biology.

Research

Overview

Research interests include molecular aspects of HIV-1 pathogenesis using the chimeric simian-human immunodeficiency virus (SHIV)/ macaque model system with specific interests in:

• molecular mechanisms through which the Vpu protein of HIV-1 contributes to the pathogenesis of the virus

• molecular mechanisms of through which the Vif protein of HIV-1 contributes to the pathogenesis of the virus

• the use of macaque models to study lentivirus infection and persistence