Endocytosed HIV-1 Envelope Glycoprotein Traffics to Rab14<sup>+</sup>Late Endosomes and Lysosomes to Regulate Surface Levels in T-Cell Lines
Huxley K. Hoffman, Rebekah S. Aguilar, Austin R. Clark, Nicholas S. Groves, Nairi Pezeshkian, Merissa M. Bruns, Schuyler B. van Engelenburg
Abstract
HIV-1 envelope glycoprotein (Env) evades immune neutralization through many mechanisms. One immune evasion strategy may result from the internalization of excess surface-exposed Env to prevent antibody-dependent cellular cytotoxicity or neutralization. Characterization of the fate of endocytosed Env is critical to understand which vesicular pathways could be targeted to promote display of Env epitopes to the immune system. In this study, we characterize the endocytic fate of native Env, expressed from infected human T-cell lines. We demonstrate that Env is rapidly trafficked to a late-endosome/lysosome-like compartment and can be recycled to the cell surface for incorporation into virus assembly sites. This study implicates a novel intracellular compartment, marked by host-cell Rab14 GTPases, for the sequestration of Env. Therapeutic approaches aimed at mobilizing this intracellular pool of Env could lead to stronger immune control of HIV-1 infection via antibody-dependent cell-mediated cytotoxicity.