Hepatitis C virus (HCV) tends to associate preferentially with high-density lipoproteins by standard ultracentrifugal fractionation of plasma from patients with chronic HCV infection

Because hepatitis C virus (HCV) has an unusually low buoyant density in plasma, we have determined whether HCV-RNA associates with specific lipoprotein classes by conventional NaCl-NaBr density solutions and whether the association is affected by viraemia. We studied 12 consecutive patients with chronic HCV and obtained four plasma lipoprotein fractions using sequential, isopycnic ultracentrifugation: very-low plus intermediate-density lipoproteins (VLDL/IDL; rho < 1.019 g ml(-1)), low-density lipoproteins (LDL; rho 1.019-1.063 g ml(-1)), high-density lipoproteins (HDL; rho 1.063-1.21 g ml(-1)) and very-high-density lipoproteins (rho > 1.21 g ml(-1), which also include bulk plasma proteins). HCV-RNA was determined in each fraction, and after two successive 10-fold dilutions, using a nested PCR of the 5' non-coding region. In 10 patients, HCV-RNA was detected in all samples, in one patient in only the HDL, and in the remaining patient in all fractions except LDL. This study confirms that HCV in plasma has a relatively low density and that much is lipoprotein associated. Moreover, we found that in most patients (9/12; 75%) the HDL fraction had the richest, or equal richest, concentration of HCV-RNA. Nevertheless, the virion clearly distributed heterogeneously in plasma, although no obvious relationship was noted between distribution patterns and either the level of viraemia or ongoing antiviral treatment. Whether this preference for association with HDL is mediated by the lipid or protein constituents of the HCV particle remains to be established. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.