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Hepatitis C virus (HCV), especially the genotype 1, is naturally resistant to the antiviral effects of interferon-alpha (IFN-α). Expression of the whole HCV genome and the NS5A protein has been suggested to interfere with the antiviral activity of IFN-α. Here we have analyzed the effect of individual or various combinations of HCV proteins on IFN-α-mediated antiviral effect against vesicular stomatitis...
Clusters of closely spaced genes are frequently present in baculovirus genomes. We report here the detailed transcriptional mapping of one such gene cluster from Bombyx mori nucleopolyhedrovirus (BmNPV) comprising five ORFs, viz., Bm42, Lef-10, VP1054, Bm44, and Bm45, which are closely spaced and transcribed in the same orientation. This region is homologous to ORFs 53, 53a, 54, 55, and 56, respectively,...
The V protein of Sendai virus (SeV) is nonessential for virus replication in cell culture but indispensable for viral pathogenicity in mice. At the C terminus of the V protein, there are amino acid residues conserved among the members of the Paramyxovinae subfamily that are clustered in three regions: region I, just downstream of the RNA editing site; and regions II and III, cysteine-rich zinc-finger-like...
We have previously reported that the hepatitis B virus X protein (HBx) activates nuclear factor of activated T cells (NF-AT), a key regulator of the immune system, by a calcium/calcineurin-dependent pathway, involving dephosphorylation and nuclear translocation of this transcription factor. In addition, we showed that HBx synergizes with potent calcium-mobilizing stimuli to activate NF-AT-dependent...
We propose a rational approach to the design of live virus vaccines against influenza infection by alteration of the influenza A virus M2 protein, which is responsible for ion channel activity. Previously we demonstrated that a mutant A/WSN/33 (H1N1) influenza virus with defective M2 ion channel activity did not show appreciable growth defects in cell culture, although its growth was attenuated in...
We have created a novel method for coupling adenoviral vectors to solid microbeads in a way that does not adversely affect the infectivity of the attached virions. This method utilizes the extremely tight interaction between the protein streptavidin and its ligand biotin as a means of tethering viral particles to microbeads. The adenovirus-microbead conjugates that were created functioned as fully...
Viral immediate-early (IE) genes are the first class of viral genes expressed during primary infection or reactivation from latency. They usually encode regulatory proteins that play crucial roles in viral life cycle. In a previous study, four regions in the KSHV genome were found to be actively transcribed in the immediate-early stage of viral reactivation in primary effusion lymphoma cells. Three...
Macrophages express both CXCR4 and CCR5 coreceptors, but restrict X4 HIV-1 replication unless the Env-V3 region, a major determinant of cell tropism, is exchanged with that of R5 HIV-1. As the V3 exchange concomitantly alters the nucleotide sequences, we introduced silent mutations in the V3 or C2 region of macrophage-tropic R5 JRFL without changing the amino acids. Immunoblot analysis confirmed that...
We have previously demonstrated that the bZIP transcription factor CREB-2, also called ATF-4, trans-activates, in association with the viral protein Tax, the human T-cell leukemia virus type I (HTLV-I) promoter. In this study, we have examined whether CREB-2 acetylation affects transcriptional activation mediated by Tax. We present evidence that CREB-2 is acetylated in vitro and in vivo. CREB-2 is...
''Norwalk-like viruses'' (NLV), a member of the family Caliciviridae, are the major causative agents of acute gastroenteritis and are genetically divided into two groups, genogroup I (GI) and genogroup II (GII). We have determined the complete nucleotide sequences of 10 new NLV strains. Using this information together with eight known NLV sequences, the criteria to further classify genotypes of NLV...
The unique chimeric organization of the white spot syndrome virus (WSSV) tk-tmk gene encodes a protein which has significant homology to both cellular-type thymidine kinase (TK) and cellular-type thymidylate kinase (TMK), but the functional activity of this protein has not been demonstrated. Because TK is usually expressed only at very low levels in host cells, in this study, the coding region of...
Genomic microarrays were used to examine the complex temporal program of gene expression exhibited by bacteriophage T4 during the course of development. The microarray data confirm the existence of distinct early, middle, and late transcriptional classes during the bacteriophage replicative cycle. This approach allows assignment of previously uncharacterized genes to specific temporal classes. The...
Human papillomavirus type 33 (HPV-33) pseudovirus infection is a slow process dependent on the initial interaction with cell-surface heparan sulfate (T. Giroglou, L. Florin, F. Schafer, R. E. Streeck, and M. Sapp, 2001a, J. Virol. 75, 1565-1570). We have now further dissected the initial steps of pseudovirus uptake using removal of cell-surface proteoglycans and selective inhibition of entry pathways...
DNA-binding and functional assays examined the role played by NF-IL6 in regulation of HIV-1 transcription in human monocyte/macrophages (U937 cells), stimulated with LPS+PMA. When incubated with nuclear extracts from stimulated cells, a region (-189/-147), containing the major NF-IL6-binding sequence and the USF site, interacted selectively with USF1 and USF2. Anti-C/EBPβ reacted poorly with the complexes...
Signal transduction pathways induced by cytokines can modulate the level of HIV-1 gene transcription and replication in a variety of cells including those from the central nervous system. Here, we investigated the effect of TGFβ-1 signaling the factors, including Smads, on transcription of the viral LTR in human astrocytic cells. Ectopic expression of Smad-3 increased activity of the viral promoter,...
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