NUCLEOTIDE-SEQUENCE DIVERSITY OF HYPERVARIABLE REGION-1 OF HEPATITIS-C VIRUS IN JAPANESE HEMOPHILIACS WITH CHRONIC HEPATITIS-C AND PATIENTSWITH CHRONIC POSTTRANSFUSTON HEPATITIS-C

Hemophiliac patients with chronic hepatitis C might be exposed to and become infected with multiple hepatitis C virus (HCV) strains by means of frequent use of blood products, even if they are infected with a s ingle subtype of HCV. To test this hypothesis, we analyzed the genetic diversity of hypervariable region 1 (HVR1) of HCV in chronically infe cted hemophiliacs and in patients with chronic posttransfusion hepatit is with a single HCV inoculation. The diversity of nucleotide sequence s in HVR1 of serum HCV RNA was compared between 21 hemophiliacs infect ed with a single HCV subtype and 16 patients with posttransfusion HCV infection. The number of HCV quasispecies was determined by fluorescen ce single-strand conformation polymorphism (SSCP) analysis. Direct seq uencing was performed to determine the diversity in HVR1. The number o f HCV quasispecies in the blood was 5.2 +/- 2.0 clones in hemophiliacs and 4.0 +/- 2.3 clones in posttransfusion patients, a nonsignificant difference (P = .0943). The number of sites at which the nucleotide wa s not homogenous in all quasispecies was significantly higher in hemop hiliacs (13.0% +/- 7.4%) than in posttransfusion hepatitis patients (2 .7% +/- 2.8%; P < .0001), In conclusion, there was a high degree of ge netic variation in HVR1 of HCV specimens isolated from hemophiliacs co mpared with posttransfusion patients. These findings indicate the poss ibility that multiple infections of a single HCV subtype may occur amo ng patients frequently exposed to blood products; single HCV subtypes may therefore derive from multiple origins. (C) 1996 by The American S ociety of Hematology.