From the Journals

Biophysical properties of HCV evolve over course of infection

 

Key clinical point: The biophysical properties of the hepatitis C virus evolve during the course of infection and shift with dietary changes.

Major finding: Density fractionation of infectious mouse serum showed higher infectivity in the low-density fractions soon after infection, but heterogeneity subsequently increased while infectivity decreased. A 5-week diet of 10% sucrose produced a minor shift toward infectivity that correlated with redistribution of triglycerides and cholesterol.

Data source: A study of 13 human liver chimeric mice.

Disclosures: Funders included the National Institutes of Health and the American Association for the Study of Liver Diseases. The investigators disclosed no conflicts.

View on the News

Lipid components of HCV particle may be targetable

A hallmark of HCV infection is the association of virus particles with lipoproteins. The HCV virion (lipo-viro particle, LVP) is composed of nucleocapsid and envelope glycoproteins associated with very-low- and low-density lipoproteins, cholesterol, and apolipoproteins. The lipid components determine the size, density, hepatotropism, and infectivity of LVPs and play a role in cell entry, morphogenesis, release, and viral escape mechanisms. LVPs undergo dynamic changes during infection, and dietary triglycerides induce alterations in their biophysical properties and infectivity.

Dr. Agata Budkowska
HCV species and tissue specificity is limited to the human hepatocyte. Since hepatoma cells in vitro produce virus particles with incomplete lipoprotein composition, mouse models with transplanted human primary hepatocytes have been developed to investigate infection in vivo.
Dr. Andreo and colleagues used humanized Fah–/– mice to analyze the evolution of HCV particles during infection. As previously reported, two viral populations of different densities were detected in mice sera, with higher infectivity observed for the low-density population. The proportions and infectivity of these populations varied during infection, reflecting changes in biochemical features of the virus. Sucrose diet influenced the properties of virus particles; these properties’ changes correlated with a redistribution of triglycerides and cholesterol among lipoproteins.

Changes in biochemical features of the virus during infection represent a fascinating aspect of the structural heterogeneity, which influences HCV infectivity and evolution of the disease. Further studies in experimental models that reproduce the lipoprotein-dependent morphogenesis and release of virus particles, maturation, and intravascular remodeling of HCV-associated lipoproteins would help to develop novel lipid-targeting inhibitors to improve existing therapies.

Agata Budkowska, PhD, is scientific advisor for the department of international affairs at the Institut Pasteur, Paris. She has no conflicts of interest.


 

FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY

 

Hepatitis C virus (HCV) particles are of lowest density and most infectious early in the course of infection, based on findings from a study of chimeric mice.

Recommended for You

News & Commentary

Quizzes from MD-IQ

Research Summaries from ClinicalEdge

Next Article: