HCV NS4B protein induces lipid accumulation through activation of
SREBPs. A, both vector and NS4B-Myc stable cells were
cotransfected with FAS-Luc reporter and Flag-SREBP-1a (1–490 amino
acids) or HA-SREBP-1c (1–447 amino acids) expression plasmids. At 36 h
after transfection, cells were harvested and then luciferase activities were
determined (top panel). Data represent the mean of two independent
experiments. ***, p < 0.001, vector stable
versus NS4B stable cells transfected with Flag-SREBP-1a.
*, p < 0.05, vector stable versus NS4B stable
cells transfected with HA-SREBP-1c. Equal amounts of cell lysates were
subjected to immunoblotting with anti-FLAG, anti-HA, anti-Myc, and
anti-β-actin monoclonal antibody (bottom panel). B,
Huh7 cells were transfected with NS4B-Myc expression plasmid. At 36 h after
transfection, cells were fixed and incubated with anti-Myc monoclonal antibody
for 2 h. After being washed with PBS, cells were further incubated with
TRITC-conjugated goat anti-mouse IgG and BODIPY 493/503 (1 μm,
Invitrogen) for 1 h. Samples were analyzed for immunofluorescence staining
using the LSM 510 laser confocal microscopy system and BODIPY intensity was
quantified. Each bar represents the average intensity of BODIPY
staining. ***, p < 0.001, NS4B-negative cells
versus NS4B-positive cells. C, Huh7 cells were either
mock-infected or infected with HCV JFH-1. At 3 days after infection, cells
were transfected with FAS-Luc reporter plasmid. At 24 h after transfection,
cells were harvested and then luciferase activities were determined.
D, at 3 days after infection, total cell lysates were immunoblotted
with either anti-FAS antibody (top panel) or anti-NS5A antibody
(middle panel). Protein expression of β-actin was used as a
loading control for the same amount of cell lysates (bottom panel).
E, at 3 days after infection, cells were fixed and incubated with
anti-NS5A polyclonal antibody for 2 h. After being washed with PBS, cells were
further incubated with TRITC-conjugated goat anti-mouse IgG and BODIPY 493/503
(1 μm, Invitrogen) for 1 h. Immunofluorescence staining was
performed as described in B. ***, p < 0.001,
mock-infected cells versus HCV-infected cells. Cells were
counterstained with 4′,6-diamidino-2-phenylindole (DAPI) to
label nuclei.