genetic heterogeneity of hepatitis c virus in association with antiviral therapy determined by ultra-deep sequencing遗传异质性的丙型肝炎病毒与抗病毒治疗取决于超深测序.pdfVIP

Genetic Heterogeneity of Hepatitis C Virus in Association with Antiviral Therapy Determined by Ultra-Deep Sequencing 1 1 1 1 1 Akihiro Nasu , Hiroyuki Marusawa *, Yoshihide Ueda , Norihiro Nishijima , Ken Takahashi , Yukio 2 3 4 5 6 6 Osaki , Yukitaka Yamashita , Tetsuro Inokuma , Takashi Tamada , Takeshi Fujiwara , Fumiaki Sato , Kazuharu Shimizu6, Tsutomu Chiba1 1 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2 Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan, 3 Department of Gastroenterology and Hepatology, Wakayama Red Cross Hospital, Wakayama, Japan, 4 Department of Gastroenterology, Kobe City Medical Center General Hospital, Kobe, Japan, 5 Department of Gastroenterology and Hepatology Takatsuki Red Cross Hospital, Osaka, Japan, 6 Department of Nanobio Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Abstract Background and Aims: The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail. Methods: Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) a2b plus ribavirin therapy. Results: Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, correspo