1.From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor.
Clinical and Molecular Hepatology 2015;21(3):193-199
Hepatitis B virus (HBV) is the prototype of hepatotropic DNA viruses (hepadnaviruses) infecting a wide range of human and non-human hosts. Previous studies with duck hepatitis B virus (DHBV) identified duck carboxypeptidase D (dCPD) as a host specific binding partner for full-length large envelope protein, and p120 as a binding partner for several truncated versions of the large envelope protein. p120 is the P protein of duck glycine decarboxylase (dGLDC) with restricted expression in DHBV infectible tissues. Several lines of evidence suggest the importance of dCPD, and especially p120, in productive DHBV infection, although neither dCPD nor p120 cDNA could confer susceptibility to DHBV infection in any cell line. Recently, sodium taurocholate cotransporting polypeptide (NTCP) has been identified as a binding partner for the N-terminus of HBV large envelope protein. Importantly, knock down and reconstitution experiments unequivocally demonstrated that NTCP is both necessary and sufficient for in vitro infection by HBV and hepatitis delta virus (HDV), an RNA virus using HBV envelope proteins for its transmission. What remains unclear is whether NTCP is the major HBV receptor in vivo. The fact that some HBV patients are homozygous with an NTCP mutation known to abolish its receptor function suggests the existence of NTCP-independent pathways of HBV entry. Also, NTCP very likely mediates just one step of the HBV entry process, with additional co-factors for productive HBV infection still to be discovered. NTCP offers a novel therapeutic target for the control of chronic HBV infection.
Animals
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Carboxypeptidases/genetics/*metabolism
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Gene Products, pol/genetics/metabolism
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Heparan Sulfate Proteoglycans/metabolism
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Hepatitis B virus/*physiology
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Hepatocytes/metabolism/virology
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Organic Anion Transporters, Sodium-Dependent/antagonists & inhibitors/genetics/metabolism
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RNA Interference
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Symporters/antagonists & inhibitors/genetics/metabolism
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Viral Envelope Proteins/metabolism
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Virus Internalization
2.An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma.
Qiujun QIU ; Sunhui CHEN ; Huining HE ; Jixiang CHEN ; Xinyi DING ; Dongdong WANG ; Jiangang YANG ; Pengcheng GUO ; Yang LI ; Jisu KIM ; Jianyong SHENG ; Chao GAO ; Bo YIN ; Shihao ZHENG ; Jianxin WANG
Acta Pharmaceutica Sinica B 2023;13(12):5091-5106
Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.