Hepatitis C virus: Morphogenesis, infection and therapy

Figure 6 Putative distribution of lipoproteins (LDL, VLDL, HDL), lipoviral particles and viral cores after density gradient centrifugation of plasma from infected individual. The picture is based on the known buoyant densities of analyzed elements[15,170,184-187]. The density values (g/mL) are given on the left. The initial material that has been used for the virus isolation, contributes greatly to the associated lipid content of the virions and, as a consequence, it influences the buoyant density[177,183-187]. Because of an irregular protein to cholesterol amounts, high density lipoproteins (HDL) of 5-15 nm in diameter can be detected in the different fractions (1.06-1.21 g/mL). The family of HDL is given as dark blue spheres. The buoyant density of microvesicles (MVs) may vary from 1.02 g/mL to 1.16 g/mL, depending on MVs diameter and cargo (miRNA, tRNA, fragments of mRNA and proteins). If hepatitis C virus (HCV) is released in MVs with similar diffusion parameters (size and mass), the buoyant density of vesicle should be viral cargo-dependent. Fractions 1: Single cellular or viral proteins “floating” on the surface, very low-density lipoproteins (VLDL, diameter 50-75 nm, density 0.95-1.006 g/mL); Fraction 2: Low density lipoproteins (LDL, diameter 18-25 nm, density 1.019-1.06 g/mL) and virus-free MVs with a low cellular cargo content; Fraction 3: MVs that carry few viral particles, possible overlap with LDL and HDL; Fraction 4: MVs with a higher viral load, possible overlaps with HDL and with densely loaded virus-free MVs; Fraction 5: Lipoviral particles (LVP, diameter 60-80 nm, density 1.10-1.16 g/mL) and MVs with a significant viral and/or mixed load. Overlaps with HDL, virus-loaded MVs and “dense” virus-free MVs are possible; Fraction 6: Lipid-free virions with attached immunoglobulins, possible overlap with HDL; Fractions 7: HDL with a high protein load; Fraction 8: Non-enveloped viral cores that might overlap with dense HDL. Small grey spheres - VLDL. Light blue spheres - LDL. Orange arrows indicated fractions of the gradient that are most likely to contain viruses and viral cores.