Analysis of Hepatitis C Virus Intrahost Diversity across the Coding Region by Ultradeep Pyrosequencing

Hepatitis C virus (HCV) is the leading cause of liver disease worldwide. In this study, we analyzed four treatment-naive patients infected with subtype 1a and performed Roche/454 pyrosequencing across the coding region. We report the presence of low-level drug resistance mutations that would most likely have been missed using conventional sequencing methods. The approach described here is broadly applicable to studies of viral diversity and could help to improve the efficacy of direct-acting antiviral agents (DAA) in the treatment of HCV-infected patients.

National Center for Research Resources (NCRR), National Institutes of Health (NIH) [P51 RR000167]

Clinical Science Research and Development Service [I01CX000117]

NIH [R01 AI077376-01, GM43940]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP 2007/53457-7, 2008/50461-6]

University of Wisconsin School of Medicine and Public Health through Wisconsin Center for Infectious Disease (WisCID)

Research and Facilities Improvement Program [RR15459-01, RR020141-01]