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Journal of Virology, July 2009, p. 6922-6928, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02674-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Kazuo Sugiyama,1* Kenji Suzuki,2 Takahide Nakazawa,3 Kenji Funami,1 Takayuki Hishiki,4 Kazuya Ogawa,4 Satoru Saito,5 Kumiko W. Shimotohno,2 Takeshi Suzuki,2 Yuko Shimizu,1 Reiri Tobita,6 Makoto Hijikata,7 Hiroshi Takaku,6 and Kunitada Shimotohno1,4

Center for Integrated Medical Research, Keio University, Shinjuku-ku, Shinanomachi 35, Tokyo 160-8582, Japan,1 Division of Basic Biological Sciences, Faculty of Pharmacy, Keio University, Tokyo 105-8512, Japan,2 Department of Gastroenterology, Internal Medicine, Kitasato University East Hospital, Kanagawa 228-8520, Japan,3 Research Institute, Chiba Institute of Technology, Chiba 275-0016, Japan,4 Yokohama City University Hospital, Kanagawa 236-0004, Japan,5 Department of Life and Environmental Sciences, Chiba Institute of Technology, Chiba 275-0016, Japan,6 Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan7

Received 29 December 2008/ Accepted 6 April 2009

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.

* Corresponding author. Mailing address: Center for Integrated Medical Research, Keio University, Shinjuku-ku, Shinanomachi 35, Tokyo 160-8582, Japan. Phone: 81-3-3353-1211. Fax: 81-47-478-0527. E-mail: sygiyamkz{at}a8.keio.jp

{triangledown} Published ahead of print on 15 April 2009.

Journal of Virology, July 2009, p. 6922-6928, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.02674-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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