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 i n plasma, we have determined whether HCV-RNA associates with specific lipoprotein classes by conventional NaCl-NaBr density solutions and wh ether the association is affected by viraemia. We studied 12 consecuti ve patients with chronic HCV and obtained four plasma lipoprotein frac tions using sequential, isopycnic ultracentrifugation: very-low plus i ntermediate-density lipoproteins (VLDL/IDL; rho < 1.019 g ml(-1)), low -density lipoproteins (LDL; rho 1.019-1.063 g ml(-1)), high-density li poproteins (HDL; rho 1.063-1.21 g ml(-1)) and very-high-density lipopr oteins (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. Thi s study confirms that HCV in plasma has a relatively low density and t hat much is lipoprotein associated. Moreover, we found that in most pa tients (9/12; 75%) the HDL fraction had the richest, or equal richest, concentration of HCV-RNA. Nevertheless, the virion clearly distribute d heterogeneously in plasma, although no obvious relationship was note d between distribution patterns and either the level of viraemia or on going antiviral treatment. Whether this preference for association wit h HDL is mediated by the lipid or protein constituents of the HCV part icle remains to be established. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.