constrained pattern of viral evolution in acute and early hcv infection limits viral plasticity限制病毒进化的模式在急性病毒性可塑性和丙肝病毒感染早期限制.pdfVIP

Constrained Pattern of Viral Evolution in Acute and Early HCV Infection Limits Viral Plasticity 1. 1,2. 3 1 3 1 Katja Pfafferott , Silvana Gaudieri , Axel Ulsenheimer , Ian James , Malte Heeg , David Nolan , Mina 1 1,4 1 1 5 3 John , Andri Rauch , Simon Mallal , Andrew Lucas , Paul Klenerman , Helmut M. Diepolder , Michaela Lucas1* 1 Centre for Clinical Immunology and Biomedical Statistics, Institute for Immunology Infectious Diseases, Murdoch University and Royal Perth Hospital, Perth, Australia, 2 School of Anatomy and Human Biology and Centre for Forensic Science, University of Western Australia, Perth, Australia, 3 Medical Department II and Institute for Immunology, Ludwig-Maximilians-University Munich, Munich, Germany, 4 University Hospital Berne and University of Berne, Berne, Switzerland, 5 Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom Abstract Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions