Hepatitis A virus VP3 may activate serum response element associated transcription.
BACKGROUND
Hepatitis A virus (HAV) infection is a major public health problem worldwide. The infection does not induce any visible cytopathic effects or interfere with macromolecular synthesis in host cells. However, the hepatitis B and C viruses have recently been reported to activate intracellular signals. To clarify the effects of HAV infection on intracellular signalling, we examined the influence of 9 FLAG-tagged HAV proteins (VP2, VP3, VP1-2A, 2B, 2C, 3A, 3BC, 3C and 3D) on signal transduction pathways.


METHODS
Viral protein expression vectors were co-transfected into HeLa cells with reporter plasmids controlled by a synthetic promoter containing direct repeats of the cyclic AMP response element (CRE), serum response factor (SRF), activator protein 1 (AP-1), nuclear factor kappaB (NF-kappaB) or serum response element (SRE). Cells were harvested 42 h after transfection and luciferase assays were performed. Viral protein activation twice that of the control was defined as significant.


RESULTS
VP3 induced an SRE-associated signal 2.2 +/- 0.3 times higher than that of control. VP3 did not activate CRE-, SRF-, AP-1- or NF-kappaB- associated signalling. The other HAV proteins tested also failed to induce these pathways.


CONCLUSIONS
HAV interacts with the host signalling mechanism, and HAV VP3, different from HBX and hepatitis C core protein, may activate only SRE-associated intracellular signalling, a pathway associated with cell proliferation and differentiation.
Dept. of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
T
T
Kanda
O
O
Yokosuka
N
N
Kato
F
F
Imazeki
K
K
Fujiwara
S
S
Kawai
H
H
Saisho
M
M
Omata
D015153:Blotting, Western; D002373:Cyclic AMP Receptor Protein / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006506:Hepatitis A / Q000378:metabolism* / Q000503:physiopathology*; D017957:Hepatitis A Virus, Human / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000502:physiology; D014176:Protein Biosynthesis; D011506:Proteins; D027602:Serum Response Element / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D014764:Viral Proteins / Q000096:biosynthesis*
D002373:Cyclic AMP Receptor Protein; D016328:NF-kappa B; D011506:Proteins; D018808:Transcription Factor AP-1; D014764:Viral Proteins; D017868:Cyclic AMP-Dependent Protein Kinases