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Human Rhinovirus

Our Research

Human rhinovirus (HRV) causes upper respiratory infections and asthma exacerbations. We screened multiple orthologous RNAi reagents and identified host proteins that modulate HRV replication. In these efforts we worked very hard to minimize the caveats of siRNA screening, false positives and false negatives using a combination of multiple orthologous RNAi reagents (MORR), informatics and detailed validation studies. This work is important because it represents a comprehensive resource of rhinovirus host interactions and is the largest single siRNA screen to date (4 orthologous RNAi libraries) with all of the primary dataset sets integrated;

Our Results

We found that this approach markedly improved both the sensitivity and the specificity of the screen, and the we detailed our methods to accomplish this, as well as how to compare the efficacy of different siRNA screens and analyses. Using this approach, we found a previously uncharacterized regulator of endocytosis, RNASEK. We determined that RNASEK was needed for the replication of all viruses tested that entered via the endocytic pathway, for example HRV, influenza A virus, and dengue virus. RNASEK was found to be required for the function of the acidifying proton pump complex, V-ATPase, with its loss resulting in decreased expression and altered localization of the V-ATPase subunits. Together, the results of our work show that RNASEK closely associates with the V-ATPase and is required for its function, with its loss preventing the early events of endocytosis and the replication of multiple pathogenic viruses.

 

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