Entry and intracellular trafficking of measles virus glycoprotein pseudotyping lentivector for transduction in target cells

Measles virus, enveloped RNA virus, infects lungs, airways, lymphocytes and multiple organs, causing respiratory disease and immune suppression. Due to the specificity of measles virus structure, recent improvements have been made on combining lentivectors, potent gene transfer vehicles, with measles virus envelope glycoproteins, allowing targeted cell entry. However, the detailed mechanism underlying either measles virus or measles virus glycoprotein pseudotyping lentivectors transduction remained unclear. In this study, we examined the transduction of lentivectors carrying measles virus glycoprotein (H/F-LV) to Vero/hSLAM cells to understand the entry and intracellular trafficking process. Results showed that H/F-LVs used clathrin mediated internalization as the major entry route before trafficking through different endosomal compartments. It was also demonstrated that microtubule network and actin filaments played active roles for H/F-LV transduction. Collectively, our findings have shed some light on the entry and intracellular pathway of measles virus pseudotyping lentivectors, which may facilitate designing antiviral targets and efficient viral vector for use in gene therapy.