within-host dynamics of the hepatitis c virus quasispecies population in hiv-1hcv coinfected patients丙型肝炎病毒的宿主中的动力学准物种人口hiv-1hcv合并感染患者.pdfVIP

Within-Host Dynamics of the Hepatitis C Virus Quasispecies Population in HIV-1/HCV Coinfected Patients 1 1 1 1 1 Flavia Bernini , Erika Ebranati , Chiara De Maddalena , Renata Shkjezi , Laura Milazzo , Alessandra Lo 2 2 1 1 Presti , Massimo Ciccozzi , Massimo Galli , Gianguglielmo Zehender * 1 Department of Clinical Sciences ‘‘L. Sacco’’, University of Milan, Milan, Italy, 2 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di ` Sanita, Rome, Italy Abstract HIV/HCV coinfected individuals under highly active antiretroviral therapy (HAART) represent an interesting model for the investigation of the role played by the immune system in driving the evolution of the HCV quasispecies. We prospectively studied the intra-host evolution of the HCV heterogeneity in 8 coinfected subjects, selected from a cohort of 32 patients initiating HAART: 5 immunological responders (group A) and 3 immunological non-responders (group B), and in two HCV singly infected controls not assuming drugs (group C). For all these subjects at least two serial samples obtained at the first observation (before HAART) and more than 1 year later, underwent clonal sequence analysis of partial E1/E2 sequences, encompassing the whole HVR1. Evolutionary rates, dated phylogenies and population dynamics were co-estimated by using a Bayesian Markov Chain Monte Carlo approach, and site specific selection pressures were estimated by maximum likelihood-based methods. The intra-host evolutionary rates of HCV quasispecies was 10 times higher in subjects treated with HAART than in controls without immunodeficiency (1.9 and 2.3 61023 sub/site/month in group