Title: "Dissecting Population Structure and Viral Fitness Landscapes in Dengue Host Adaptation"
Speaker: Patrick Dolan; Department of Biology, Stanford University, Stanford, CA

Place: LILLY Hall G126
Date: November 3, 2015; Tuesday
Time: 4:30pm

Abstract:
Dengue virus (DENV) is a rapidly emerging, mosquito-transmitted human pathogen that accounts for 100 million infections annually. DENV's human and mosquito hosts differ significantly in cellular metabolism, antiviral immunity, and temperature and these differences shape unique fitness landscapes that the virus must traverse within each. Using a high-resolution sequencing technique, circular resequencing (CirSeq), we have mapped the changes in viral sequence and population structure over the course of serial passage in human and mosquito cells. Our analysis has revealed key mutations in both coding and non-coding regions of the viral genome that facilitate viral replication in its alternative hosts. Further, we have used our population sequencing data to describe and visualize an experimentally-derived genotype-fitness landscape for human and mosquito cells, and show that these fitness landscapes, inferred from sequencing data alone, correspond well to observed phenotypic adaptation.

Associated reading:
A. Acevedo, L. Brodsky, and R. Andino. 2014. Mutational and fitness landscapes of an RNA virus revealed through population sequencing. Nature. 505:686-690, include supplemental methods.


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