reconstructing the dynamics of hiv evolution within hosts from serial deep sequence data主机内重建hiv的动力学演化系列深度序列数据.pdfVIP

Reconstructing the Dynamics of HIV Evolution within Hosts from Serial Deep Sequence Data 1 1 2,3 2,4 2,4 Art F. Y. Poon *, Luke C. Swenson , Evelien M. Bunnik , Diana Edo-Matas , Hanneke Schuitemaker , ´ 2,4, P. Richard Harrigan1 Angelique B. van ’t Wout 1 BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada, 2 Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 3 Department of Cell Biology and Neuroscience, University of California, Riverside, California, United States of America, 4 Crucell Holland BV, Leiden, The Netherlands Abstract At the early stage of infection, human immunodeficiency virus (HIV)-1 predominantly uses the CCR5 coreceptor for host cell entry. The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of progression to AIDS. The presence of a ‘fitness valley’ separating CCR5- and CXCR4-using genotypes is postulated to be a biological determinant of whether the HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the evolutionary dynamics of HIV within hosts enables us to discriminate between competing models of this process. We have developed a phylogenetic pipeline for the molecular clock analysis, ancestral reconstruction, and visualization of deep sequence data. These data were generated by next- generation sequencing of HIV RNA extracted