From DCPD to NTCP: The long journey towards identifying a functional hepatitis B virus receptor

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.

Relationship between chemosensitivity in vitro and the expression of GRP78 in non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>The expressive level of glucose-regulated protein 78 (GRP78) is elevated and correlated with resistance of chemotherapy drugs in breast cancer cell. However, little is known about the relationship between its expression and drug resistance in non-small cell lung cancer (NSCLC). The aim of this study was to explore the relationship between drug resistance and the expression of GRP78 in NSCLC.</p><p><b>METHODS</b>Drug sensitivity test was used to detect the resistance to 8 chemotherapy drugs in 52 NSCLC fresh surgical samples by methylthiazoletrazolium (MTT), and expression of GRP78 was detected by immunohistochemistry method. Spearman correlation assay was used to investigate the correlation between the GRP78 expression and drug resistance.</p><p><b>RESULTS</b>The resistance rates to paclitaxel (PTX), adriamycin (ADM), carboplatin (CBP), topotecan (TPT), navelbine (NVB), vincristine (VCR), cisplatin (DDP) and etoposide (VP-16) of the 52 samples were 42.31%, 57.69%, 63.46%, 65.38%, 67.31%, 73.08%, 78.85%, 90.38%, respectively. Fourteen cases showed the complete resistance to the total 8 chemotherapy drugs. Furthermore, the expression of GRP78 was stronger in poorly differentiated cancer as compared with the well and moderately differentiated cancer (P < 0.05), so as in stage II and III cancer than in stage I cancer (P < 0.05). Spearman correlation assay showed that there was a correlation between the chemotherapeutics resistance to ADM, VP-16, VCR, TPT and the expression of GRP78 in NSCLC (P < 0.05).</p><p><b>CONCLUSIONS</b>It is feasible to detect the drug sensitivity to chemotherapy for tumor cells by MTT method. The results of chemosensitivity assay in vitro are indicative of clinical drug administration in NSCLC. The detection of GRP78 isalso indicative of the resistance to chemotherapy drugs and the differentiation and the clinical stage in NSCLC.</p>