Herpes simplex virus type 1 glycoprotein M (gM) is a type III membrane protein conserved throughout the family Herpesviridae. However, despite this conservation, gM is classed as a non-essential protein in most alphaherpesviruses. Previous data have suggested that gM is involved in secondary envelopment, although how gM functions in this process is unknown. Using transfection-based assays, we have previously shown that gM is able to mediate the internalization and subcellular targeting of other viral envelope proteins, suggesting a possible role for gM in localizing herpesvirus envelope proteins to sites of secondary envelopment. To investigate the role of gM in infected cells, we have now analysed viral envelope protein localization and virion incorporation in cells infected with a gM-deletion virus or its revertant. In the absence of gM expression, we observed a substantial inhibition of glycoprotein H-L (gH-L) internalization from the surface of infected cells. Although deletion of gM does not affect expression of gH and gL, virions assembled in the absence of gM demonstrated significantly reduced levels of gH-L, correlating with defects of the gM-negative virus in entry and cell-to-cell spread. These data suggest an important role of gM in mediating the specific internalization and efficient targeting of gH-L to sites of secondary envelopment in infected cells.
Epigenetics has been implicated in human cancer development. Epigenetic factors include HBx protein, which is able to induce hypermethylation and suppresses tumor suppressor genes. One of such tumor suppressor genes, GSTP1, shows reduced expression in many human cancers. Hypermethylation of GSTP1 is the most studied mechanism of its silence. In the present study, we reported that GSTP1 expression was completely depleted in HBV integrated HepG2.2.15 cells due to the hypermethylation in its promoter region. And it was HBx, especially HBx genotype D, that played the key role in repressing GSTP1 expression. Further functional studies like ROS assay and apoptosis detection were also used to confirm this repression. Our findings should facilitate the understanding of HBV and their influences on the epigenetic modulations for epigenetic tumorigenesis during HBV-mediated hepatocellular carcinogenesis.
Exercise preconditioning (EP) attenuates pathological cardiac hypertrophy by increasing the functional capacity of the cardiovascular system; however, the underlying molecular mechanisms remain unclear. MicroRNAs (miRNAs) play important roles in various physiological and pathological processes by regulating the expression of the targeted gene. In this study, we aimed to screen the miRNAs involved in EP-attenuating pathological cardiac hypertrophy. The histological and echocardiographic parameters assessment showed that pathological cardiac hypertrophy induced by transverse aortic constriction (TAC) was significantly alleviated in EP treated rats. The left ventricular tissues (n = 3) from Sham, TAC and EP + TAC groups were subjected to small RNA deep sequencing. A total of 570 known mature miRNAs and 530 putative novel miRNAs were detected. DEGseq analysis showed that there were 37 and 88 differentially expressed miRNAs in the comparisons of TAC versus Sham and EP + TAC versus TAC, respectively. Among them, EP treatment could relieve the expression changes of 32 miRNAs, which were supposed to be involved in EP-attenuating pathological cardiac hypertrophy. After miRNAs target genes prediction by miRDB algorithm, pathway analysis showed that the most frequently represented pathways were involved in Calcium signaling pathway and MAPK signaling pathway. The results would provide valuable clues to finding therapeutic targets for the treatment of pathological cardiac hypertrophy.
Inhibitors of Hepatitis B Virus. -A variety of 1-sulfonyl-2-aminobenzimidazole derivatives [cf. (V), (VII), (XIV)] issynthesized and evaluated for anti-hepatitis B virus (HBV) activity and cytotoxicity in vitro. Most of them are potential HBV inhibitors with high selectivity indices. Derivatives (Vd) and (VII) appear to be the most promising compounds. -(LI, Y.-F.; WANG, G.-F.; LUO, Y.; HUANG, W.-G.; TANG, W.; FENG, C.-L.; SHI, L.-P.; REN, Y.-D.; ZUO, J.-P.; LU*, W.; Eur.
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