David T. Evans, PhD

Professor of Pathology and Laboratory Medicine

Areas of investigation in Dr. David Evans’ laboratory include lentiviral resistance to tetherin (BST-2 or CD317),  the role of viral peptides in modulating natural killer (NK) cell activation through KIR-MHC class I interactions, and mechanisms of HIV-1 resistance to antibody-dependent cell-mediated cytotoxicity (ADCC). Tetherin is an interferon-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. They found that Vpu protects HIV-1 infected cells from ADCC as a function of its ability to counteract tetherin (Arias et al. PNAS. 2015. PMID: 24733916). These results imply that tetherin serves as a link between innate and adaptive immunity to enhance the susceptibility of virus-infected cells to antibodies, suggesting that the antiviral activity of tetherin in vivo may be much greater than previously appreciated based on its ability to inhibit virus release in cell culture assays. They also identified peptides of SIV and HIV-1 that suppress NK cell responses by stabilizing the binding of common MHC class I molecules to inhibitory KIRs, revealing a mechanism by which immunodeficiency viruses may evade NK cell responses (Schafer et al. PLoS Pathog. 2015. PMID: 26333068; van Teijlingen et al. AIDS. 2014. PMID: 24785948; Hölzemer et al. PLoS Med. 2015. PMID: 26575988). As part of his thesis research in Dr. Evans’ laboratory, Benjamin von Bredow demonstrated a correlation between the ability of HIV-1 Env-specific antibodies to kill virus-infected cells by ADCC and to neutralize virus infectivity, indicating that the same structural features of the Env trimer that confer resistance to neutralization also protect virus-infected cells from elimination by antibodies (von Bredow et al. J. Virol. 2016. PMID: 27122574). Dr. von Bredow is currently a postdoctoral trainee in clinical microbiology at Pennsylvania State College of Medicine, Hershey, PA. Dr. Evans’ group collaborates with Drs. D. O’Connor, S. O’Connor, Friedrich and Reynolds (Schafer et al. J. Immunol. 2014. PMID: 24453246; Arias et al. J. Virol. 2016. PMID: 27654287; Ries et al. PLoS Pathog. 2017. PMID: 28708886; Banerjee et al. J. Immunol. 2018. In press). Dr. Evan’s lab is supported by an R01 for which he is PI, an R33, the Primate Center P51, and a grant from the Dana Farber Cancer Institute/Gilead Sciences.