Expression of autophagy-modulating genes in peripheral blood mononuclear cells from familial clustering patients with chronic hepatitis B virus infection
We previously found that genetic factors are associated with a familial predisposition for developing liver cirrhosis and hepatocellular carcinoma during chronic hepatitis B virus (HBV) infection. Autophagy has been shown to play a role in HBV replication and the course of disease. More than 190 host genes have been identified that modify the process of autophagy, but which of these genes are involved in chronicity of HBV infection and how this occurs remains unclear. Chronic hepatitis B (CHB) patients were recruited to investigate the expression of autophagy-modulating genes in peripheral blood mononuclear cells (PBMCs). mRNA prepared from PBMCs from members of two families with clustering HBV infection, including 11 CHB patients and nine healthy spouses, was hybridized to high-density oligonucleotide arrays. Immunoblot analysis was used to determine the level of autophagy. Of the 192 autophagy-modulating genes, 18 were found to be differently expressed. Of these, 11 displayed decreased expression in CHB patients, while seven displayed increased expression compared to those in healthy controls. Functional analysis showed that these genes are closely involved in initiation, nucleation, elongation of phagophores, formation of autophagosomes, transportation to lysosomes, and the process of degradation. Western blot analysis revealed inhibited autophagy in PBMCs based on decreased lipidation of LC3II. A differential expression profile of autophagy-modulating genes was observed, and decreased autophagy in PBMCs could be closely associated with chronicity of HBV infection, suggesting a novel strategy for the treatment of patients with chronic HBV infection.
This work was financially supported by the National Natural Science Foundation of China (No. 81570528) and the National 13th Five-Year Special Grand Project for Infectious Diseases of China (No. 2016ZX10002007). In addition, Zhen Tian wants to thank, in particular, the care, patience and love from Shiyuan Yang.
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Conflict of interest
The authors whose names are listed below certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria, educational grants, participation in speakers’ bureaus, membership, employment, consultancies, stock ownership, or other equity interest, and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript. We have no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Human Research Ethics Committee from the First Affiliated Hospital of Xi’an Jiaotong University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was received from all participants before the study.
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