The Journal of Infectious Diseases 2010;202:000–000
© 2010 by the Infectious Diseases Society of America. All rights reserved.
Jennifer A.Smith, 1 Judith H. Aberle, 4 Vicki M. Fleming, 2 Peter Ferenci, 5 Emma C. Thomson, 3 Peter Karayiannis, 3 Angela R. McLean, 1 Heidemarie Holzmann, 4 and Paul Klenerman 2
1 Institute for Emerging Infections and 2 Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, and 3 Department of Hepatology, Imperial College, London, United Kingdom; 4 Institute of Virology and 5 Department of Internal Medicine, Gastroenterology, and Hepatology, Medical University of Vienna, Vienna, Austria
Introduction.Acute hepatitis C virus (HCV) infection is rarely studied, but virus sequence evolution and host‐virus dynamics during this early stage may influence the outcome of infection. Hypervariable region 1 (HVR1) is genetically diverse and under selective pressure from the host immune response. We analyzed HVR1 evolution by frequent sampling of an acutely infected HCV cohort.
Methods.Three or more pretreatment samples were obtained from each of 10 acutely infected subjects. Polymerase chain reaction amplification was performed with multiple primer combinations to identify the full range of sequences present. Positive samples were cloned and sequenced. Phylogenetic analyses were used to assess viral diversity.
Results.Eight of the 10 subjects were coinfected with at least 2 HCV subtypes. Multiple subtypes were detected in individual samples, and their relative proportions changed through acute infection. The subjects with the most complex subtype structure also had a dynamic viral load; however, changes in viral load were not directly linked to changes in subtype.
Conclusions.This well‐sampled cohort with acute HCV infection was characterized by dynamic coinfection with multiple viral subtypes, representing a highly complex virologic landscape extremely early in infection.
Received 18 January 2010; accepted 19 July 2010; electronically published 10 November 2010.
(See the editorial commentary by Irving and Brown, on pages XXX–XXX.)
Reprints or correspondence: Prof Paul Klenerman, Peter Medawar Building for Pathogen Research, South Parks Rd, Oxford OX1 3SY, United Kingdom (firstname.lastname@example.org).
Potential conflicts of interest: none reported.
Presented in part: Epidemics Conference, Monterey, California, 1–3 December 2008 (oral presentation).
Financial support: Wellcome Trust; Medical Research Council; James Martin 21st Century School, Oxford; US National Institutes of Health (grant U19 AI082630); UK National Institute for Health Research Biomedical Research Centre Programme, Oxford.