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Sci Rep. 2015 Nov 20;5:16459. doi: 10.1038/srep16459.

Hepatitis B virus spliced variants are associated with an impaired response to interferon therapy.

Author information

1
Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, China.
2
Shanghai Public Health Clinical Center, Shanghai Medical College of Fudan University, China.
3
Huashan Hospital affiliated to Fudan University, China.
4
Institutes of Medical Microbiology and Biomedical Sciences, Fudan University, Shanghai, China.

Abstract

During hepatitis B virus (HBV) replication, spliced HBV genomes and splice-generated proteins have been widely described, however, their biological and clinical significance remains to be defined. Here, an elevation of the proportion of HBV spliced variants in the sera of patients with chronic hepatitis B (CHB) is shown to correlate with an impaired respond to interferon-α (IFN-α) therapy. Transfection of the constructs encoding the three most dominant species of spliced variants into cells or ectopic expression of the two major spliced protein including HBSP and N-terminal-truncated viral polymerase protein result in strong suppression of IFN-α signaling transduction, while mutation of the major splicing-related sites of HBV attenuates the viral anti-IFN activities in both cell and mouse models. These results have associated the productions of HBV spliced variants with the failure response to IFN therapy and illuminate a novel mechanism where spliced viral products are employed to resist IFN-mediated host defense.

PMID:
26585041
PMCID:
PMC4653653
DOI:
10.1038/srep16459
[Indexed for MEDLINE]
Free PMC Article

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