Genetic Analysis of Hepatitis C Virus with Defective Genome and Its Infectivity in Vitro

Author:

Sugiyama Kazuo1,Suzuki Kenji2,Nakazawa Takahide3,Funami Kenji1,Hishiki Takayuki4,Ogawa Kazuya4,Saito Satoru5,Shimotohno Kumiko W.2,Suzuki Takeshi2,Shimizu Yuko1,Tobita Reiri6,Hijikata Makoto7,Takaku Hiroshi6,Shimotohno Kunitada14

Affiliation:

1. Center for Integrated Medical Research, Keio University, Shinjuku-ku, Shinanomachi 35, Tokyo 160-8582, Japan

2. Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan

3. Department of Gastroenterology, Internal Medicine, Kitasato University East Hospital, Kanagawa 228-8520, Japan

4. Research Institute, Chiba Institute of Technology, Chiba 275-0016, Japan

5. Yokohama City University Hospital, Kanagawa 236-0004, Japan

6. Department of Life and Environmental Sciences, Chiba Institute of Technology, Chiba 275-0016, Japan

7. Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan

Abstract

ABSTRACT Replication and infectivity of hepatitis C virus (HCV) with a defective genome is ambiguous. We molecularly cloned 38 HCV isolates with defective genomes from 18 patient sera. The structural regions were widely deleted, with the 5′ untranslated, core, and NS3-NS5B regions preserved. All of the deletions were in frame, indicating that they are translatable to the authentic terminus. Phylogenetic analyses showed self-replication of the defective genomes independent of full genomes. We generated a defective genome of chimeric HCV to mimic the defective isolate in the serum. By using this, we demonstrated for the first time that the defective genome, as it is circulating in the blood, can be encapsidated as an infectious particle by trans complementation of the structural proteins.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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