The Interferon-Inducible Human PLSCR1 Protein Is a Restriction Factor of Human Cytomegalovirus.

Human phospholipid scramblase 1 (PLSCR1) is strongly expressed in response to interferon (IFN) treatment and viral infection, and it has been suggested to play an important role in IFN-dependent antiviral responses. In this study, we showed that the levels of human cytomegalovirus (HCMV) plaque formation in OUMS-36T-3 (36T-3) cells with high basal expression of PLSCR1 were significantly lower than those in human embryonic lung (HEL) cells with low basal expression of PLSCR1. In addition, the levels of HCMV plaque formation and replication in PLSCR1-knockout (KO) 36T-3 cells were significantly higher than those in parental 36T-3 cells and were comparable to those in HEL cells.

The anti-human cytomegalovirus drug tricin inhibits cyclin-dependent kinase 9.

4',5,7-trihydroxy-3',5'-dimethoxyflavone (tricin), derived from , has been reported to suppress significantly human cytomegalovirus (HCMV) replication in human embryonic lung (HEL) fibroblast cells. However, the target protein of tricin remains unclear. This study focused on the anti-HCMV activity of tricin in terms of its binding affinity to cyclin-dependent kinase 9 (CDK9).

Tricin inhibits the CCL5 induction required for efficient growth of human cytomegalovirus.

Treatment of human embryonic lung fibroblast (HEL) cells with tricin (4', 5, 7-trihydroxy-3', 5'-dimethoxyflavone) following infection with human cytomegalovirus (HCMV) reportedly significantly suppresses HCMV replication. In the present work, the mechanisms for the anti-HCMV effects of tricin in HEL cells were examined. It was found that exposure of HEL cells to tricin inhibited HCMV replication, with concomitant decreases in amounts of transcripts of the CC chemokine RANTES (CCL5)-encoding gene and in expression of the CCL5 protein.

An in silico-designed flavone derivative, 6-fluoro-4'-hydroxy-3',5'-dimetoxyflavone, has a greater anti-human cytomegalovirus effect than ganciclovir in infected cells.

A novel type of antiviral agent for human cytomegalovirus (HCMV) is required, because the appearance of ganciclovir (GCV) resistant viruses has been reported. Tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) has been shown to suppress significantly HCMV replication in human embryonic lung (HEL) fibroblast cells. Recently, we revealed that the action of tricin is different from that of GCV and cyclin-dependent kinase 9 (CDK9) is one of the target proteins of tricin.

Inhibition of human cytomegalovirus replication by tricin is associated with depressed CCL2 expression.

We previously reported that treatment with tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone) after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virion production and HCMV replication in human embryonic lung fibroblast (HEL) cells. Moreover, we recently demonstrated that HCMV infection can increase the expression of CC-motif ligand 2 (CCL2/MCP-1) and of CCR2, a CCL2-specific receptor, effects that can in turn enhance HCMV infection and replication. Hence, we here examined whether the CCL2-CCR2 axis is involved in the anti-HCMV effects of tricin in HEL cells.

Regulation of Matrix Metalloproteinases-2 and -9 Gene Expression in Cultured Human Fetal Membrane Cells by Influenza Virus Infection.

In order to understand a possible etiology of adverse pregnancy outcomes associated with intrauterine influenza virus infection, we examined the effect of influenza virus infection on gene expression of matrix metalloproteinases (MMPs) in cultured amnion epithelial, amnion mesenchymal and chorion trophoblast cells prepared from human fetal membrane tissues by gelatin zymography, Western blotting and reverse transcriptase-PCR. The cells were infected with influenza A (H1N1) virus. The levels of pro-MMP-9 activity in culture supernatants of three types of cells were increased during the period of 24-48 h after the virus infection as compared to those of mock infection.

Synergistic effects by combination of ganciclovir and tricin on human cytomegalovirus replication in vitro.

It has been demonstrated as the first report that combination treatment with ganciclovir (GCV) and tricin (4',5,7-trihydroxy-3',5' -dimethoxyflavone), a derivative of Sasa albo-marginata, after human cytomegalovirus (HCMV) infection has synergistic effects on both infectious virus production and HCMV DNA synthesis in the human embryonic fibroblast cell line MRC-5. In this paper, we examined the anti-HCMV effects of GCV plus various concentrations of tricin, and tricin plus various concentrations of GCV in MRC-5 cells. We found that expression of the HCMV UL54 gene was significantly inhibited by combination of GCV with tricin when compared with GCV mono-treatment.

Molecular analysis of the tlyA gene in Campylobacter lari.

Full-length tlyA gene and its adjacent genetic loci from the urease-positive thermophilic Campylobacter (UPTC) CF89-12 [approximately 15,000 base pairs (bp) in length], as well as a reference strain Campylobacter lari RM2100 (approximately 9,000 bp), were analyzed. The possible open-reading frame of tlyA from UPTC CF89-12 was shown to have 720 bp with a calculated molecular mass of approximately 26.7 kDa.

Human cytomegalovirus replication supported by virus-induced activation of CCL2-CCR2 interactions.

We previously revealed that human cytomegalovirus (HCMV) infection can cause aberrant expression of the chemokine IL-8/CXCL8. We first examined the effects of HCMV infection on the expression of another chemokine, CCL2. HCMV infection induced CCL2 expression at the mRNA and protein levels in human embryonic lung fibroblasts cells (HEL).

Transgenic rice seed synthesizing diverse flavonoids at high levels: a new platform for flavonoid production with associated health benefits.

Flavonoids possess diverse health-promoting benefits but are nearly absent from rice, because most of the genes encoding enzymes for flavonoid biosynthesis are not expressed in rice seeds. In the present study, a transgenic rice plant producing several classes of flavonoids in seeds was developed by introducing multiple genes encoding enzymes involved in flavonoid synthesis, from phenylalanine to the target flavonoids, into rice. Rice accumulating naringenin was developed by introducing phenylalanine ammonia lyase (PAL) and chalcone synthase (CHS) genes.

Anti-cytomegalovirus effects of tricin are dependent on CXCL11.

It has been reported that treatment with tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone), a derivative of Sasa albo-marginata, after human cytomegalovirus (HCMV) infection significantly suppressed both infectious virus production and HCMV replication in the human embryonic fibroblast cell line MRC-5. In this paper, we examined the mechanisms for the anti-HCMV effects of tricin in MRC-5 cells. Exposure of fibroblasts to tricin inhibited infectious HCMV production, with concomitant decreases in levels of transcripts of the CXC chemokine IFN-inducible T cell alpha chemoattractant (I-TAC or CXCL11) gene.

Herpes simplex virus requires poly(ADP-ribose) polymerase activity for efficient replication and induces extracellular signal-related kinase-dependent phosphorylation and ICP0-dependent nuclear localization of tankyrase 1.

Tankyrase 1 is a poly(ADP-ribose) polymerase (PARP) which localizes to multiple subcellular sites, including telomeres and mitotic centrosomes. Poly(ADP-ribosyl)ation of the nuclear mitotic apparatus (NuMA) protein by tankyrase 1 during mitosis is essential for sister telomere resolution and mitotic spindle pole formation. In interphase cells, tankyrase 1 resides in the cytoplasm, and its role therein is not well understood.

Anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone.

Background: We examined the anti-influenza virus activity of tricin, 4',5,7-trihydroxy-3',5'-dimethoxyflavone, against five viruses: A/Solomon islands/3/2006 (H1N1), A/Hiroshima/52/2005 (H3N2), A/California/07/2009 (H1N1pdm), A/Narita/1/2009 (H1N1pdm) and B/Malaysia/2506/2004 strains in vitro and against A/PR/8/34 virus in vivo.

Methods: The effect of tricin was studied by an infectious virus yield reduction assay. The anti-influenza virus mechanism of the tricin was examined by western blot analysis, real-time reverse transcriptase PCR analysis, haemagglutination inhibition (HI) assay and neuraminidase (NA) inhibition assay.

Inhibitory effects of tricin derivative from Sasa albo-marginata on replication of human cytomegalovirus.

The anti-human cytomegalovirus (HCMV) activity of tricin (4',5,7-trihydroxy-3',5'-dimethoxyflavone), a derivative from Sasa albo-marginata, was studied in the human embryonic fibroblast cell line MRC-5. In a plaque assay, tricin and ganciclovir (GCV) showed concentration-dependent inhibitory properties from 0.05 to 3.

UL146 variability among clinical isolates of human cytomegalovirus from Japan.

Human cytomegalovirus (HCMV) is a herpesvirus associated with serious diseases in immunocompromised subjects. The region between ORF UL133 and UL151 from HCMV, named ULb' is frequently deleted in attenuated AD169 and in highly passaged laboratory strains. However, this region is conserved in low-passaged and more virulent HCMV, like the Toledo strain.

Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner.

Human antibodies specific for HCMV are currently considered as potential anti-HCMV therapeutic agents. In this study, we used a combinatorial human antibody library to isolate and characterize complete human monoclonal antibodies that effectively neutralize HCMV in a complement-dependent manner. One hundred and six clones were isolated in two independent screens using HCMV virions and recombinant glycoprotein B, gB654, as antigens.

Proteasome inhibitor differentially regulates expression of the major immediate early genes of human cytomegalovirus in human central nervous system-derived cell lines.

Proteasome inhibitor, which inhibits NF-kappaB activation, has been reported to activate c-Jun N-terminal kinase (JNK)-c-Jun pathway. In this study, we investigated the effects of proteasome inhibitor on the human cytomegalovirus (HCMV) major immediate early (MIE) gene expression in human central nervous system (CNS)-derived cell lines. Treatment of HCMV-infected 118MGC glioma and U373-MG astrocytoma cells with three proteasome inhibitors, MG132, clasto-lactacystin beta-lactone, and epoxomicin, suppressed MIE protein expression.

Anticytomegalovirus activity of pristimerin, a triterpenoid quinone methide isolated from Maytenus heterophylla (Eckl. & Zeyh.).

We examined the anticytomegalovirus properties of four compounds: pristimerin, the pristimerin analogue, lupeol and 2-acetylphenol-1-beta-D-glucopyranosyl (1 --> 6)-beta-D-xylpyranoside (acetophenol glycoside), isolated from Maytenus heterophylla, a Kenyan medicinal plant. The effects were studied on human cytomegalovirus (HCMV) replication in the human embryonic fibroblast cell line, MRC-5. In a viral plaque-reduction assay, pristimerin showed dose-dependent inhibitory properties with a 50% inhibitory concentration of 0.

Inhibition of ganciclovir-resistant human cytomegalovirus replication by Kampo (Japanese herbal medicine).

We examined the effect of Kampo on the replication of ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) in the human embryonic fibroblast cell line MRC-5. Treatment of HCMV-infected cells with Sho-seiryu-to (SST; Xiao-Qing-Long-Tang in Chinese) resulted in the inhibition of viral replication without affecting the cell growth. SST treatment decreased the synthesis of viral DNA, but had no virucidal effect on cell-free HCMV.

In Vitro Anti-Cytomegalovirus Activity of Kampo (Japanese Herbal) Medicine.

We examined the effect of three types of Kampo medicines on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with at least 0.01 mug/ml of Kampo medicines inhibited the cytopathic effects of CMV-infected MRC-5 cells.

Analysis of human cytomegalovirus UL144 variability in low-passage clinical isolates in Japan.

To explore a possible role for viral genes as determinants of virulence, portions of the UL144 tumor necrosis factor-like receptor gene and the UL55 envelope glycoprotein B gene from 42 patients with congenital human cytomegalovirus (HCMV) infection or other diseases were sequenced. Of the 42 patients, 16 (38%) had UL144 group 1 [group 1A, 15 of 16 (94%); group 1B, 1 of 16 (6%); group 1C, 0 of 16 (0%)], 5 patients (12%) had UL144 group 2, and 21 patients (50%) had UL144 group 3. Although group 1C was not found in Japan strains (0%), it was found in USA strains (22%).

2,3,7,8-Tetrachlorodibenzo-p-dioxin is a possible activator of human cytomegalovirus replication in a human fibroblast cell line.

We examined the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with 0.0001pg/ml TCDD augmented the cytopathic effects of CMV-infected MRC-5 cells.