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Cell Rep. 2015 Aug 4;12(5):850-63. doi: 10.1016/j.celrep.2015.06.076. Epub 2015 Jul 23.

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

Author information

  • 1Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA.
  • 2Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
  • 3Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA. Electronic address: abraham.brass@umassmed.edu.

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.

PMID:
26212330
DOI:
10.1016/j.celrep.2015.06.076
[PubMed - indexed for MEDLINE]
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