Detection of a 5′ end subgenome of hepatitis C virus terminating at nucleotide 384 in patients' plasma and liver tissues

Quadri and Negro [Dig Liver Dis 2001; 33: 480] reported greater distribution of 5′ end genomic RNA of hepatitis C virus (HCV) over its 3′ end in the liver of patients with recurrent hepatitis C after liver transplantation. We not only confirmed their results by quantifying the 5′ end subgenomes in various specimens by using dilution and real‐time polymerase chain reaction methods, but also discovered that such subgenomes terminated at nucleotide (nt) 384 of the viral genome or in its immediate upstream. The subgenomes in the plasma uniformly, with a few exceptions, ended at this position, while those in the liver more heterogeneously at various points upstream of nt 384. Subgenome populations ending some points in the downstream of nt 384 were not detected. The amount of the 5′ end subgenome, while fluctuating during the clinical course of the patients, exceeded that of the longer sized HCV genomes which included the intact genome, and, when the relative ratio of the 5′ end subgenome increased, the amount of longer sized HCV RNA tended to decrease, suggesting a suppressive effect of the 5′ end subgenome on viral replication.