Single-cell delineation of strain-specific HIV-1 Vif activities using dual reporter sensor cells and live cell imaging

Abstract

Human immunodeficiency virus type 1 (HIV-1) is highly heterogeneous and constantly mutating. These changes drive immune evasion and can cause treatment efforts to fail. Here, we describe the “dual reporter sensor cell” (DRSC) assay; a novel imaging-based approach that allows for the detection of HIV-1 infection coupled with a multivariate definition of several independent phenotypic aspects of viral genome activity in a single integrated assay. We validate the DRSC system by studying lab-adapted and patient isolate-derived versions of the viral Vif accessory protein, confirming marked differences in the capacity of diverse vif alleles to mediate downregulation of antiviral APOBEC3G proteins and dysregulate the cell cycle.