Department of Microbiology and Physiological Systems
Cellular and Molecular Physiology | Microbial Physiology | Pathogenic Microbiology | Virology
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.
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Copyright © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
DOI of Published Version
Cell Rep. 2015 Aug 4;12(5):850-63. doi: 10.1016/j.celrep.2015.06.076. Epub 2015 Jul 23. Link to article on publisher's site
Perreira, Jill; Aker, Aaron; Savidis, George; Chin, Christopher R.; McDougall, William M.; Portmann, Jocelyn M.; Meraner, Paul; Smith, Miles; Rahman, Motiur; Baker, Richard E.; Gauthier, Annick; Franti, Michael; and Brass, Abraham L., "RNASEK Is a V-ATPase-Associated Factor Required for Endocytosis and the Replication of Rhinovirus, Influenza A Virus, and Dengue Virus" (2015). Open Access Articles. 2625.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.