Genetic analysis of hepatitis C virus with defective genome and its infectivity in vitro.
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.
Center for Integrated Medical Research, Keio University, Shinjuku-ku, Shinanomachi 35, Tokyo 160-8582, Japan. sygiyamkz@a8.keio.jp
Kazuo
K
Sugiyama
Kenji
K
Suzuki
Takahide
T
Nakazawa
Kenji
K
Funami
Takayuki
T
Hishiki
Kazuya
K
Ogawa
Satoru
S
Saito
Kumiko W
KW
Shimotohno
Takeshi
T
Suzuki
Yuko
Y
Shimizu
Reiri
R
Tobita
Makoto
M
Hijikata
Hiroshi
H
Takaku
Kunitada
K
Shimotohno
D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D017423:Sequence Analysis, RNA; D017384:Sequence Deletion; D019065:Virus Assembly
D012367:RNA, Viral