Pathology and Laboratory Medicine Department
Host-pathogen interactions for HIV and SIV
585 Science Dr
Madison, WI 53711
My research program is directed towards understanding host-pathogen interactions for human and simian immunodeficiency viruses. Current areas of investigation include mechanisms of lentiviral resistance to tetherin/BST-2, the role of killer-cell immunoglobulin-like receptor (KIR) and MHC class I interactions in regulating natural killer (NK) cell responses, and antibody-dependent cell-mediated cytotoxicity (ADCC) as a mechanism of protective immunity. Recent studies from my lab have contributed to our understanding of the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in immunodeficiency virus infection. We developed an assay for measuring the ability of antibodies to direct the killing of HIV-1- and SIV-infected cells expressing native conformations of the viral envelope glycoprotein (Alpert et al. J. Virol. 2012). For its physiological relevance, sensitivity, broad dynamic range, and reproducibility, this assay was selected as one of six primary variables for the immune correlates analysis of the RV144 (or “Thai trial”) vaccine trial (Haynes et al. N. Engl. J. Med. 2012). Using this assay, we found also that the time-dependent maturation of complete protection in macaques immunized with nef-deleted, live-attenuated SIV is associated with progressive increases in ADCC activity against the challenge virus (Alpert et al. PLoS Pathog. 2012). More recently, we reported a general correlation between ADCC and virus neutralization by HIV-1 Env-specific monoclonal antibodies (von Bredow et al. J. Virol. 2016), which indicates, perhaps not surprisingly, that most antibodies that are able to bind to functional Env trimers on virions to block infectivity are also able to bind to Env on the surface of virus-infected cells to direct their elimination by ADCC; however, this correlation was imperfect revealing specific differences in Env epitopes exposed on the surface of infected cells and virions.