Mutations in interferon sensitivity determining region of hepatitis C virus: Its relation to change in viral load

OBJECTIVE: Interferon sensitivity-determining region (ISDR) in nonstructura l region 5A of hepatitis C virus (HCV) genotype-lb has been reported to be associated with viral load. Viral load is usually small in the patients wit h mutant type (four or more amino acid substitutions, compared with HCV-J) and large in those with wild (identical to HCV-J) or intermediate type (fro m one to three amino acid substitutions). A possible correlation was invest igated between mutations in ISDR and alterations of viral load during the c ourse of disease. METHODS: The sequences of ISDR were determined in eight patients with signi ficant changes of viral load and in 11 patients without changes. RESULTS: In two of the eight patients with significant alterations of viral load, ISDR sequences changed significantly. In one patient whose viral loa d increased after a course of interferon therapy, the number of substitutio ns, compared with HCV-J, decreased from five to zero or one; the type of IS DR converted from mutant type to wild or intermediate type. In one patient whose viral load decreased significantly after two courses of interferon th erapy, the number of substitutions increased from one to six; ISDR changed from intermediate type to mutant type. In the remaining six patients with c hanges of viral load and in the other 11 patients without changes, the sequ ences of ISDR did not change significantly. CONCLUSIONS: The mutations in ISDR are one of the viral factors involved in the changes in viral load during the course of disease, although the major ity of other factors involved are still unknown. (C) 2000 by Am. Coll. of G astroenterology).