RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the Replication of Rhinovirus, Influenza A Virus, and Dengue Virus

  • Cell Rep. 2015 Aug 4;12(5):850-63. doi: 10.1016/j.celrep.2015.06.076.
Jill M Perreira  1 ,  Aaron M Aker  1 ,  George Savidis  1 ,  Christopher R Chin  1 ,  William M McDougall  1 ,  Jocelyn M Portmann  1 ,  Paul Meraner  1 ,  Miles C Smith  1 ,  Motiur Rahman  1 ,  Richard E Baker  1 ,  Annick Gauthier  2 ,  Michael Franti  2 ,  Abraham L Brass  3
Affiliations
  • 1. Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
  • 2. Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
  • 3. Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA. Electronic address: [email protected].
PMID: 26212330 DOI: 10.1016/j.celrep.2015.06.076
Abstract

Human rhinovirus (HRV) causes upper respiratory infections and asthma exacerbations. We screened multiple orthologous RNAi reagents and identified host proteins that modulate HRV replication. Here, we show that RNASEK, a transmembrane protein, was needed for the replication of HRV, influenza A virus, and Dengue Virus. RNASEK localizes to the cell surface and endosomal pathway and closely associates with the vacuolar ATPase (V-ATPase) Proton Pump. RNASEK is required for endocytosis, and its depletion produces enlarged clathrin-coated pits (CCPs) at the cell surface. These enlarged CCPs contain endocytic cargo and are bound by the scissioning GTPase, DNM2. Loss of RNASEK alters the localization of multiple V-ATPase subunits and lowers the levels of the ATP6AP1 subunit. Together, our results show that RNASEK closely associates with the V-ATPase and is required for its function; its loss prevents the early events of endocytosis and the replication of multiple pathogenic viruses.