Functional interplay between hepatitis B virus X protein and human miR-125a in HBV infection.
The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). Some cellular microRNAs are emerging as important regulators of virus-host interaction, indirectly or directly modulating HBV replication and pathogenesis. miR-125a binds the viral transcript encoding the surface antigen and interferes with its expression, thus inhibiting viral replication. Intriguingly, liver miR-125a expression has been found increased in patients with high levels of hepatic HBV-DNA. The present study investigates the mechanism by which liver exposure to HBV induces the expression of miR-125a. The analyses were first performed on liver biopsies from HBV patients, showing that the expression of the viral transactivator X protein (HBx) paralleled the increase of miR-125a expression. Then, transfection of HCC cell lines with an HBx-expressing vector showed a substantial increase of miR-125a expression. Overall, the available data depict a self-inhibitory feedback loop in which HBV, through HBx, increases the expression of miR-125a, that in turn interferes with expression of HBV surface antigen, thus repressing viral replication.
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. Electronic address: nicola.mosca@unina2.it.
Nicola
N
Mosca
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. Electronic address: filomena.castiello@unina2.it.
Filomena
F
Castiello
Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni 5, 80135 Naples, Italy. Electronic address: nicola.coppola@unina2.it.
Nicola
N
Coppola
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. Electronic address: mconsigliatrotta@gmail.com.
Maria Consiglia
MC
Trotta
Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni 5, 80135 Naples, Italy. Electronic address: caterina.sagnelli@unina2.it.
Caterina
C
Sagnelli
Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni 5, 80135 Naples, Italy. Electronic address: meri.pisaturo@libero.it.
Mariantonietta
M
Pisaturo
Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, via L. Armanni 5, 80135 Naples, Italy. Electronic address: evangelista.sagnelli@unina2.it.
Evangelista
E
Sagnelli
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. Electronic address: aniello.russo@unina2.it.
Aniello
A
Russo
Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, via Vivaldi 43, 81100 Caserta, Italy. Electronic address: nicoletta.potenza@unina2.it.
Nicoletta
N
Potenza
D000328:Adult; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology* / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000276:immunology*; D008875:Middle Aged; D011485:Protein Binding; D014018:Tissue Distribution; D015534:Trans-Activators / Q000276:immunology*; D019562:Viral Load / Q000276:immunology*; D054334:Viral Regulatory and Accessory Proteins
C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
Hepatocellular carcinoma; Molecular mechanisms; Viral hepatitis; miR-125a