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

Jill M. Perreira; Aaron M. Aker; George Savidis; Christopher R. Chin; William M. McDougall; Jocelyn M. Portmann; Paul Meraner; Miles C. Smith; Motiur Rahman; Richard E. Baker; Annick Gauthier; Michael Franti; Abraham L. Brass

doi:10.1016/j.celrep.2015.06.076

Cell Reports (Aug 2015)

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

Jill M. Perreira,
Aaron M. Aker,
George Savidis,
Christopher R. Chin,
William M. McDougall,
Jocelyn M. Portmann,
Paul Meraner,
Miles C. Smith,
Motiur Rahman,
Richard E. Baker,
Annick Gauthier,
Michael Franti,
Abraham L. Brass

Affiliations

Jill M. Perreira: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Aaron M. Aker: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
George Savidis: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Christopher R. Chin: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
William M. McDougall: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Jocelyn M. Portmann: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Paul Meraner: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Miles C. Smith: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Motiur Rahman: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Richard E. Baker: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA
Annick Gauthier: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
Michael Franti: Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
Abraham L. Brass: Microbiology and Physiological Systems Department, University of Massachusetts Medical School, University of Massachusetts, Worcester, MA 01655, USA

DOI: https://doi.org/10.1016/j.celrep.2015.06.076
Journal volume & issue: Vol. 12, no. 5
pp. 850 – 863

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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