High levels of subgenomic HCV plasma RNA in immunosilent infections.
A genetic analysis of hepatitis C virus (HCV) in rare blood donors who remained HCV seronegative despite long-term high-level viremia revealed the chronic presence of HCV genomes with large in frame deletions in their structural genes. Full-length HCV genomes were only detected as minority variants. In one immunodeficiency virus (HIV) co-infected donor the truncated HCV genome transiently decreased in frequency concomitant with delayed seroconversion and re-emerged following partial seroreversion. The long-term production of heavily truncated HCV genomes in vivo suggests that these viruses retained the necessary elements for RNA replication while the deleted structural functions necessary for their spread in vivo was provided in trans by wild-type helper virus in co-infected cells. The absence of immunological pressure and a high viral load may therefore promote the emergence of truncated HCV subgenomic replicons in vivo.
Bernardin
Flavien
F
Blood Systems Research Institute, San Francisco, CA 94118, USA.
Stramer
Susan L
SL
Rehermann
Barbara
B
Page-Shafer
Kimberly
K
Cooper
Stewart
S
Bangsberg
David R
DR
Hahn
Judith
J
Tobler
Leslie
L
Busch
Michael
M
Delwart
Eric
E
D016679:Genome, Viral; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D008969:Molecular Sequence Data; D010949:Plasma / Q000821:virology*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015678:Viral Structural Proteins / Q000235:genetics
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D015678:Viral Structural Proteins