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.
Sugiyama
Kazuo
K
Center for Integrated Medical Research, Keio University, Shinjuku-ku, Shinanomachi 35, Tokyo 160-8582, Japan. sygiyamkz@a8.keio.jp
Suzuki
Kenji
K
Nakazawa
Takahide
T
Funami
Kenji
K
Hishiki
Takayuki
T
Ogawa
Kazuya
K
Saito
Satoru
S
Shimotohno
Kumiko W
KW
Suzuki
Takeshi
T
Shimizu
Yuko
Y
Tobita
Reiri
R
Hijikata
Makoto
M
Takaku
Hiroshi
H
Shimotohno
Kunitada
K
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