Abstract:
:Flavopiridol, roscovitine, and other inhibitors of Cyclin-Dependent Kinases (CDK) inhibit the replication of a variety of viruses in vitro while proving nontoxic in human clinical trials of their effects against cancer. Consequently, these and other Pharmacological CDK inhibitors (PCIs) have been proposed as potential antivirals. Flavopiridol potently inhibits all tested CDKs and inhibits the transcription of most cellular and viral genes. In contrast, roscovitine and other purine PCIs inhibit with high potency only CDK1, CDK2, CDK5, and CDK7, and they specifically inhibit the expression of viral but not cellular genes. The levels at which purine PCIs inhibit gene expression are unknown, as are the factors which determine their specificity for expression of viral but not cellular genes. We show herein that roscovitine prevents the initiation of transcription of herpes simplex virus type 1 (HSV-1) genes but has no effect on transcription elongation. We further show that roscovitine does not inhibit the initiation or elongation of cellular transcription and that its inhibitory effects are specific for promoters in HSV-1 genomes. Therefore, we have identified a novel biological activity for PCIs, i.e., their ability to prevent the initiation of transcription. We have also identified genome location as one of the factors that determine whether the transcription of a given gene is inhibited by roscovitine. The activities of roscovitine on viral transcription resemble one of the antiherpesvirus activities of alpha interferon and could be used as a model for the development of novel antivirals. The genome-specific effects of roscovitine may also be important for its development against virus-induced cancers.
journal_name
J Viroljournal_title
Journal of virologyauthors
Diwan P,Lacasse JJ,Schang LMdoi
10.1128/JVI.78.17.9352-9365.2004subject
Has Abstractpub_date
2004-09-01 00:00:00pages
9352-65issue
17eissn
0022-538Xissn
1098-5514pii
78/17/9352journal_volume
78pub_type
杂志文章abstract::Superinfection exclusion is the ability of an established viral infection to interfere with a second viral infection. Using West Nile virus (WNV) as a model, we show that replicating replicons in BHK-21 cells suppress subsequent WNV infection. The WNV replicon also suppresses superinfections of other flaviviruses but ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01205-09
更新日期:2009-11-01 00:00:00
abstract::The intracellular assembly site for flaviviruses in currently not known but is presumed to be located within the lumen of the rough endoplasmic reticulum (RER). Building on previous studies involving immunofluorescence (IF) and cryoimmunoelectron microscopy of Kunjin virus (KUN)-infected cells, we sought to identify t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.22.10787-10799.2001
更新日期:2001-11-01 00:00:00
abstract::Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal disease. The cp biot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.10.4692-4698.2001
更新日期:2001-05-01 00:00:00
abstract::Sapelovirus is a member of the family Picornaviridae and is emerging as an enteric porcine, simian, and avian pathogen. Here, we report the genome sequence of a novel porcine sapelovirus strain YC2011 isolated from piglets with severe diarrhea. The availability of the genome sequence is helpful to further investigatio...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01799-12
更新日期:2012-10-01 00:00:00
abstract::HTG2 hamster cells produce a defective murine sarcoma virus lacking gp70 and, consequently, viral surface projections (knobs), but the lack of knobs appears to have no effect on intramembrane particle distribution. In addition, it has been noted that the core of the virus remains in the "immature" form as a result of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.872-877.1980
更新日期:1980-12-01 00:00:00
abstract::Thirty-six monoclonal antibodies from mice and three from rats were raised against a peptide corresponding to the immunodominant domain of the transmembrane gp41 protein of human immunodeficiency virus (HIV) type 1 (LGLWGCSGKLIC; amino acid residues 598 to 609). Of these, three monoclonal antibodies from the mice and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.4.1727-1734.1991
更新日期:1991-04-01 00:00:00
abstract::The membrane glycoproteins Gn and Gc of Hantaan virus (HTNV) (family Bunyaviridae) are modified by N-linked glycosylation. The glycoproteins contain six potential sites for the attachment of N-linked oligosaccharides, five sites on Gn and one on Gc. The properties of the N-linked oligosaccharide chains were analyzed b...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.10.5414-5422.2004
更新日期:2004-05-01 00:00:00
abstract::To investigate a possible role of p53 in DNA exchange mechanisms, we have developed a model system which allows us to quantify homologous recombination rates in eukaryotic cells. We generated two types of simian virus 40 (SV40) whose genomes were mutated in such a way that upon double infection of monkey cells, virus ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.2.737-744.1996
更新日期:1996-02-01 00:00:00
abstract::The Vif protein of human immunodeficiency virus type 1 (HIV-1) is important for virion infectivity. Previous studies have shown that vif-defective virions exhibit structural abnormalities in the virus core and are defective in the ability to complete proviral DNA synthesis in acutely infected cells. We developed novel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.23.11055-11066.2000
更新日期:2000-12-01 00:00:00
abstract::ICP0, one of the five immediate-early (IE) gene products of herpes simplex virus (HSV), is a potent activator of transcription. To assess the biological activities of ICP0 and to explore its mechanisms of action, two helper-independent recombinant adenoviruses were constructed. In each recombinant, the E1 region was s...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.12.4544-4553.1988
更新日期:1988-12-01 00:00:00
abstract::As potential targets for human immunodeficiency virus type 1 and simian immunodeficiency virus (HIV-1 and SIV), dendritic cells (DCs) likely play a significant role in the onset and spread of infection as well as in the induction of antiviral immunity. Using the SIV-macaque system to study the very early events in DC-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.6.2936-2951.2002
更新日期:2002-03-01 00:00:00
abstract::Primate lentiviruses use chemokine coreceptors in addition to the CD4 receptor to initiate virus infection. Simian immunodeficiency virus (SIV) productively infects human cells expressing CD4 and the human allele of the chemokine coreceptor CCR-5 as efficiently as it infects macaque cells expressing human CD4, suggest...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.5.3932-3939.1997
更新日期:1997-05-01 00:00:00
abstract::We assessed the prediction that access of the viral NS1 protein to cellular PDZ domain protein networks enhances the virulence of highly pathogenic avian influenza A viruses. The NS1 proteins of most avian influenza viruses bear the C-terminal ligand sequence Glu-Ser-Glu-Val (ESEV) for PDZ domains present in multiple ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00610-10
更新日期:2010-10-01 00:00:00
abstract::We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T-lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expre...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5513-5523.1991
更新日期:1991-10-01 00:00:00
abstract::HIV-1 transmission occurs mainly through mucosal tissues. During mucosal transmission, HIV-1 preferentially infects α4β7+ gut-homing CCR7- CD4+ effector/effector memory T cells (TEM) and results in massive depletion of these cells and other subsets of TEM in gut-associated lymphoid tissues. However, besides being elim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01510-17
更新日期:2018-03-28 00:00:00
abstract::PM2 DNA was prepared with different superhelical densities (sigma) in order to examine the relationship betweenn supercoiling and the occurrence of a region(s) of unpaired bases in this DNA. A previous study showed that CH3HgOH reacts with native superhelical PM2 DNA more rapidly than the nicked form II. This evaluati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.1.195-204.1976
更新日期:1976-04-01 00:00:00
abstract::Adenovirus deletion mutants were studied to examine the influence of the 5' untranslated sequence on the translation of early region 1A mRNAs. Alterations of the 5' untranslated sequence, including complete deletion of the wild-type 5' untranslated sequence, did not significantly affect the rate of translation. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.3.884-888.1984
更新日期:1984-09-01 00:00:00
abstract::Previous studies have established that chlorella viruses encode K(+) channels with different structural and functional properties. In the current study, we exploit the different sensitivities of these channels to Cs(+) to determine if the membrane depolarization observed during virus infection is caused by the activit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.5.2437-2444.2006
更新日期:2006-03-01 00:00:00
abstract::The molecular defect in the nonconditional B-tropic MuLV pol mutant, clone 23 (Gerwin et al., J. Virol. 31:741-751, 1979), has been characterized by recombinant DNA technology. The entire mutant genome was cloned from an EcoRI digest of integrated cellular DNA into bacteriophage lambda Charon 4A and then subcloned at ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.2.470-478.1984
更新日期:1984-08-01 00:00:00
abstract::West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus of global importance. Neuroinvasive WNV infection results in encephalitis and can lead to prolonged neurological impairment or death. Type I interferon (IFN-I) is crucial for promoting antiviral defenses through the induction of antiviral effectors, whic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01778-18
更新日期:2019-03-05 00:00:00
abstract::The T-helper cell response to the internal proteins of rabies virus was investigated. The rabies virus nucleoprotein was shown to be a major target antigen for T-helper cells that cross-react between rabies and rabies-related viruses. T-helper cells were assayed in vitro by testing virus-induced lymphocytes for lympho...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.7.2885-2892.1989
更新日期:1989-07-01 00:00:00
abstract:UNLABELLED:Noroviruses are the leading cause of acute gastroenteritis outbreaks worldwide. The majority of norovirus outbreaks are caused by genogroup II.4 (GII.4). Novel GII.4 strains emerge every 2 to 4 years and replace older variants as the dominant norovirus. Novel variants emerge through a combination of recombin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02494-14
更新日期:2014-12-01 00:00:00
abstract:UNLABELLED:To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) regulatory protein ICP0 promotes viral gene expression and replication, we screened cells overexpressing ICP0 for ICP0-binding host cell proteins. Tandem affinity purification of transiently expressed ICP0 coupled with mass spe...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03043-15
更新日期:2016-01-06 00:00:00
abstract::In an attempt to identify the molecules involved in the pathogenesis of prion diseases, we performed cDNA subtraction on the brain tissues of mice affected with an experimental prion disease and the unaffected control. The genes identified as being upregulated in the prion-affected brain tissue included those encoding...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.1.411-417.2000
更新日期:2000-01-01 00:00:00
abstract::Herpes simplex virus (HSV) glycoprotein B (gB) is an integral part of the multicomponent fusion system required for virus entry and cell-cell fusion. Here we investigated the mechanism of viral neutralization by the monoclonal antibody (MAb) 2c, which specifically recognizes the gB of HSV type 1 (HSV-1) and HSV-2. Bin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01924-10
更新日期:2011-02-01 00:00:00
abstract::The herpes simplex virus type 1 UL28 gene contains a 785-amino-acid open reading frame that codes for an essential protein. Studies with temperature-sensitive mutants which map to the UL28 gene indicate that the UL28 gene product (ICP18.5) is required for packaging of viral DNA and for expression of viral glycoprotein...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.6.3470-3480.1993
更新日期:1993-06-01 00:00:00
abstract::Transcription of herpesviral late genes is stimulated after the onset of viral DNA replication but otherwise restricted. Late gene expression in gammaherpesviruses requires the coordination of six early viral proteins, termed viral transactivation factors (vTFs). Here, we mapped the organization of this protein comple...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02157-15
更新日期:2015-10-14 00:00:00
abstract::The complete genomic sequence of a new Muscovy duck-origin reovirus (N-MDRV), strain J18 from China, was determined. The virus has a tricistronic S1 genome segment that is distinct from the originally described MDRV, which possesses a bicistronic S4 genome segment. Pairwise comparisons and phylogenetic analyses sugges...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02230-12
更新日期:2012-11-01 00:00:00
abstract::Virion protein 16 (VP16) of herpes simplex virus type 1 (HSV-1) is a potent transcriptional activator of viral immediate-early (IE) genes. The VP16 activation domain can recruit various transcriptional coactivators to target gene promoters. However, the role of transcriptional coactivators in HSV-1 IE gene expression ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02349-08
更新日期:2009-04-01 00:00:00
abstract::Retroviral integration has recently been shown to be nonrandom, favoring transcriptionally active regions of chromatin. However, the mechanism for integration site selection by retroviruses is not clear. We show here the occurrence of Alu-like motifs in the sequences flanking the reported viral integration sites that ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01405-06
更新日期:2007-06-01 00:00:00