title: Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system.
abstract: Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity.
authors.affiliation: Hepatitis C Laboratory, CNRS-Institut de Biologie de Lille (UMR8161) and Institut Pasteur de Lille, Lille, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Lavie
authors.forename: Cécile
authors.initials: C
authors.lastname: Voisset
authors.forename: Ngoc
authors.initials: N
authors.lastname: Vu-Dac
authors.forename: Virginie
authors.initials: V
authors.lastname: Zurawski
authors.forename: Gilles
authors.initials: G
authors.lastname: Duverlie
authors.forename: Czeslaw
authors.initials: C
authors.lastname: Wychowski
authors.forename: Jean
authors.initials: J
authors.lastname: Dubuisson
mesh_terms: D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000097:blood; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology; D051122:Scavenger Receptors, Class B / Q000502:physiology; D000685:Serum Amyloid A Protein / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D000685:Serum Amyloid A Protein