Hepatitis B Virus-Encoded MicroRNA Controls Viral Replication

Viral transformation Viral Interference
DOI: 10.1128/jvi.01919-16 Publication Date: 2017-02-02T01:50:18Z
ABSTRACT
MicroRNAs (miRNAs) are a class of small, single-stranded, noncoding, functional RNAs. Hepatitis B virus (HBV) is an enveloped DNA with virions and subviral forms particles that lack core. It was not known whether HBV encodes miRNAs. Here, we identified HBV-encoded miRNA (called HBV-miR-3) by deep sequencing Northern blotting. HBV-miR-3 located at nucleotides (nt) 373 to 393 the genome generated from 3.5-kb, 2.4-kb, 2.1-kb in classic biogenesis (Drosha-Dicer-dependent) manner. highly expressed hepatoma cell lines integrated HBV+ tumors. In patients infection, released into circulation exosomes virions, expression had positive correlation titers sera acute phase infection. More interestingly, found represses HBsAg, HBeAg, replication HBV. targets unique site 3.5-kb transcript specifically reduce HBc protein expression, levels pregenomic RNA (pgRNA), intermediate (HBV-RI) generation but does affect polymerase level, thus suppressing virion production (replication). This may explain low abundant lacking core during replication, which contribute development persistent infection patients. Taken together, our findings shed light on novel mechanisms controls process self-replication regulating infection.IMPORTANCE liver caused hepatitis can become long-term, chronic lead cirrhosis or cancer. small belongs hepadnavirus family, MicroRNA (miRNA), (∼22-nt) noncoding RNA, recently be important regulator gene expression. We (HBV-miR-3). importantly, revealed its transcripts attenuate replication. explaining how leads mild damage cells subsequent establishment/maintenance Our highlight mechanism itself might provide new biomarkers for diagnosis treatment B.
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