Abstract:
:Enviroxime is an antienterovirus compound that targets viral protein 3A and/or 3AB and suppresses a step in enterovirus replication by unknown mechanism. To date, four antienterovirus compounds, i.e., GW5074, Flt3 inhibitor II, TTP-8307, and AN-12-H5, are known to have similar mutations in the 3A protein-encoding region causing resistance to enviroxime (a G5318A [3A-Ala70Thr] mutation in poliovirus [PV]) and are considered enviroxime-like compounds. Recently, antienterovirus activity of a phosphatidylinositol 4-kinase III beta (PI4KB) inhibitor, PIK93, was reported, suggesting that PI4KB is an important host factor targetable by antienterovirus compounds (N. Y. Hsu et al., Cell 141:799-811, 2010). In this study, we analyzed the inhibitory effects of previously identified enviroxime-like compounds (GW5074 and AN-12-H5) and a newly identified antienterovirus compound, T-00127-HEV1, on phosphoinositide (PI) kinases. We found that T-00127-HEV1 inhibited PI4KB activity with a higher specificity for than other PI kinases, in contrast to GW5074, which had a broad specificity for PI kinases. In contrast, AN-12-H5 showed no inhibitory effect on PI4KB activity and only moderate inhibitory effects on PI 3-kinase activity. Small interfering RNA (siRNA) screening targeting PI kinases identified PI4KB is a target of GW5074 and T-00127-HEV1, but not of AN-12-H5, for anti-PV activity. Interestingly, T-00127-HEV1 and GW5074 did not inhibit hepatitis C virus (HCV) replication, in contrast to a strong inhibitory effect of AN-12-H5. These results suggested that PI4KB is an enterovirus-specific host factor required for the replication process and targeted by some enviroxime-like compounds (T-00127-HEV1 and GW5074) and that enviroxime-like compounds may have targets other than PI kinases for their antiviral effect.
journal_name
J Viroljournal_title
Journal of virologyauthors
Arita M,Kojima H,Nagano T,Okabe T,Wakita T,Shimizu Hdoi
10.1128/JVI.02249-10subject
Has Abstractpub_date
2011-03-01 00:00:00pages
2364-72issue
5eissn
0022-538Xissn
1098-5514pii
JVI.02249-10journal_volume
85pub_type
杂志文章abstract::The small envelope protein of hepatitis B virus is the major component of the viral coat and is also secreted from cells as a 20-nm subviral particle, even in the absence of other viral proteins. Such empty envelope particles are composed of approximately 100 copies of this polypeptide and host-derived lipids and are ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4588-4597.1993
更新日期:1993-08-01 00:00:00
abstract::The 104-S monoclonal antibody immunoprecipitated from herpes simplex virus type 2 (HSV-2)-infected cell extracts the 75,000-molecular-weight glycoprotein gF and its 65,000-molecular-weight precursor (pgF). The precursor pgF was sensitive to endoglycosidase H digestion, indicating the presence of high mannose-type olig...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.47.1.185-192.1983
更新日期:1983-07-01 00:00:00
abstract::During the course of experiments designed to isolate deletion mutants of herpes simplex virus type 1 in the gene encoding the major DNA-binding protein, ICP8, a mutant, d61, that grew efficiently in ICP8-expressing Vero cells but not in normal Vero cells was isolated (P. K. Orberg and P. A. Schaffer, J. Virol. 61:1136...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.11.3528-3535.1987
更新日期:1987-11-01 00:00:00
abstract::We have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (GSHV), a nonpathogenic member of the hepadnavirus group. The genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis B viruse...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.2.367-375.1984
更新日期:1984-08-01 00:00:00
abstract::DNA polymerase activity was detected in each of eight preparations of concentrated human hepatitis B antigen (HBAg) rich in Dane particles prepared by high-speed centrifugation of antigen-positive human plasma and in none of seven control preparations prepared in the same way from HBAg-negative plasma. The incorporati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.5.995-1005.1973
更新日期:1973-11-01 00:00:00
abstract::Human cytomegalovirus-induced DNA polymerase and cellular DNA polymerase alpha were purified by successive chromatography on DEAE-cellulose, phosphocellulose, heparin agarose, and single-stranded DNA agarose columns. The purified virus-induced DNA polymerase was resolved to consist of two polypeptides corresponding to...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.3.846-851.1985
更新日期:1985-12-01 00:00:00
abstract::The virion host shutoff protein (vhs) of herpes simplex virus (HSV) triggers global shutoff of host protein synthesis and accelerated mRNA turnover during virus infection and induces endoribonucleolytic cleavage of exogenous RNA substrates when it is produced in a rabbit reticulocyte (RRL) in vitro translation system....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.3.1172-1185.2001
更新日期:2001-02-01 00:00:00
abstract:UNLABELLED:STING has emerged in recent years as a key player in orchestrating innate immune responses to cytosolic DNA and RNA derived from pathogens. However, the regulation of STING still remains poorly defined. In the present study, we investigated the mechanism of the regulation of STING expression in relation to t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00748-16
更新日期:2016-09-29 00:00:00
abstract::The emergence of antiretroviral (ARV) drug-resistant human immunodeficiency virus type 1 (HIV-1) quasispecies is a major cause of treatment failure. These variants are usually replaced by drug-sensitive ones when the selective pressure of the drugs is removed, as the former have reduced fitness in a drug-free environm...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.14.7000-7009.2002
更新日期:2002-07-01 00:00:00
abstract::To study fundamental aspects of RNA recombination, an in vivo RNA recombination system was established. This system allowed the efficient generation of recombinant cytopathogenic pestiviruses after transfection of synthetic, nonreplicatable, subgenomic transcripts in cells infected with a replicating noncytopathogenic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.12.6271-6281.2004
更新日期:2004-06-01 00:00:00
abstract::The UL16 protein of herpes simplex virus is capsid associated and was previously identified as a binding partner of the membrane-associated UL11 tegument protein (J. S. Loomis, R. J. Courtney, and J. W. Wills, J. Virol. 77:11417-11424, 2003). In those studies, a less-prominent, approximately 65-kDa binding partner of ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02015-09
更新日期:2010-03-01 00:00:00
abstract::Hepatitis B virus (HBV) DNA clones were propagated from 57 carriers with antibody to hepatitis B e antigen (HBeAg) and sequenced within nucleotides (nt) 1685 to 1926 including the core promoter (nt 1742 to 1849) and the pre-C region (nt 1814 to 1900). Mutations in the core promoter or those in the pre-C region, or bot...
journal_title:Journal of virology
pub_type: 临床试验,杂志文章
doi:10.1128/JVI.68.12.8102-8110.1994
更新日期:1994-12-01 00:00:00
abstract::Viral infection triggers host innate immune responses through cellular sensor molecules which activate multiple signaling cascades that induce the production of interferons (IFN) and other cytokines. The recent identification of mammalian cytoplasmic viral RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-li...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00404-09
更新日期:2009-08-01 00:00:00
abstract::A selection strategy, the activator trap, was used in order to identify genes of human cytomegalovirus (HCMV) that encode strong transcriptional activation domains in mammalian cells. This approach is based on the isolation of activation domains from a GAL4 fusion library by means of selective plasmid replication, whi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.10.4836-4847.2002
更新日期:2002-05-01 00:00:00
abstract::Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) is a cytokine that is poorly secreted and localized largely to the endoplasmic reticulum (ER). It has been implicated, along with other HHV-8 proinflammatory and/or angiogenic viral proteins, in HHV-8-associated Kaposi's sarcoma, primary effusion lymphoma (PEL), ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00909-20
更新日期:2020-09-15 00:00:00
abstract::Upon stimulation with alpha/beta interferon, rat cells synthesize three Mx proteins. Sequence analysis of corresponding cDNAs reveals that these three proteins are derived from three distinct genes. One of the rat cDNAs is termed Mx1 because it is most closely related to the mouse Mx1 cDNA and because it codes for a n...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.12.6263-6269.1990
更新日期:1990-12-01 00:00:00
abstract::We observed two patterns of chemokine expression in the lungs of mice infected with murine gammaherpesvirus 68: peaks of chemokine expression correlated with or occurred after the peak of viral gene expression. Chemokine expression remained elevated through 29 days postinfection. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.20.10518-10523.2002
更新日期:2002-10-01 00:00:00
abstract:UNLABELLED:Human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two major causative agents for hand-foot-and-mouth disease (HFMD). Previously, we demonstrated that a virus-like particle (VLP) for EV71 produced from Saccharomyces cerevisiae is a potential vaccine candidate against EV71 infection, and an EV...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00422-15
更新日期:2015-06-01 00:00:00
abstract::Although monkey B virus (herpesvirus simiae; BV) is common in all macaque species, fatal human infections appear to be associated with exposure to rhesus macaques (Macaca mulatta), suggesting that BV isolates from rhesus monkeys may be more lethal to nonmacaques than are BV strains indigenous to other macaque species....
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.11.9224-9232.1998
更新日期:1998-11-01 00:00:00
abstract::The neutralizing activities of polyclonal antibodies and monoclonal antibodies (MAbs) obtained by immunization of mice with L1 virus-like particles (VLPs) were investigated by using pseudovirion infectivity assays for human papillomavirus type 16 (HPV-16), HPV-31, HPV-33, HPV-45, HPV-58, and HPV-59 to obtain a better ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.13.6480-6486.2002
更新日期:2002-07-01 00:00:00
abstract::TMC125 is a potent new investigational nonnucleoside reverse transcriptase inhibitor (NNRTI) that is active against human immunodeficiency virus type 1 (HIV-1) with resistance to currently licensed NNRTIs. Sequential passage experiments with both wild-type virus and NNRTI-resistant virus were performed to identify mut...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.20.12773-12782.2005
更新日期:2005-10-01 00:00:00
abstract::T7 early mRNA's are generated from a high-molecular-weight precursor RNA by site-specific RNase III cleavage. When T7 DNA is transcribed in vitro by Escherichia coli RNA polymerase, the transcript is a large, single-piece RNA equivalent to the in vivo precursor RNA. The T7 RNA synthesized in vitro can be translated as...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.18.3.1155-1159.1976
更新日期:1976-06-01 00:00:00
abstract::The role of the influenza A virus panhandle structure formed from the 3'- and 5'-terminal nucleotides of virion RNA segments was studied in both an RNA polymerase binding assay and an in vitro transcription assay. Despite recent indications that promoter activity is simply a function of the 3'-terminal sequence of vir...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.6.4092-4096.1994
更新日期:1994-06-01 00:00:00
abstract::Varicella-zoster virus (VZV) glycoprotein I (gI) is dispensable in cell culture; the SCIDhu model of VZV pathogenesis was used to determine whether gI is necessary in vivo. The parental and repaired viruses grew in human skin and thymus/liver implants, but the gI deletion mutant was not infectious. Thus, gI is essenti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.16.8468-8471.2002
更新日期:2002-08-01 00:00:00
abstract::It was recently shown that the 7a protein of severe acute respiratory syndrome coronavirus induces biochemical changes associated with apoptosis. In this study, the mechanism by which the 7a protein induces apoptosis was examined. The 7a protein was tested for the ability to inhibit cellular gene expression because se...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.2.785-793.2006
更新日期:2006-01-01 00:00:00
abstract::Hepatitis C virus (HCV) infection remains a major worldwide health problem despite development of highly effective direct-acting antivirals. HCV rapidly evolves upon acute infection and generates multiple viral variants (quasispecies), leading to immune evasion and persistent viral infection. Identification of epitope...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00622-20
更新日期:2020-08-17 00:00:00
abstract::Resistance to erythroleukemia induced by infection with the Friend virus complex (FV) has been mapped to several genes residing both within and outside the murine major histocompatibility complex (MHC). MHC genes located in the A, D, and Qa/Tla regions of the murine H-2 complex have been shown to affect disease resist...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.8.4921-4926.1994
更新日期:1994-08-01 00:00:00
abstract::Coronavirus nonstructural protein 8 (nsp8) has been suggested to have diverse activities, including noncanonical template-dependent polymerase activities. Here, we characterized a recombinant form of the human coronavirus 229E (HCoV-229E) nsp8 and found that the protein has metal ion-dependent RNA 3'-terminal adenylyl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00291-19
更新日期:2019-05-29 00:00:00
abstract::Herpesviruses are capable of several types of infection of a host cell. To investigate the early events which ultimately determine the nature of the virus-host cell interaction, a system was established utilizing temperature-sensitive mutants of herpes simplex virus type 2. Four mutants have been isolated which fail t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.15.4.812-819.1975
更新日期:1975-04-01 00:00:00
abstract::Human papillomavirus type 16 (HPV16) is the primary etiologic agent for cervical cancer. The infectious entry of HPV16 into cells occurs via a so-far poorly characterized clathrin- and caveolin-independent endocytic pathway, which involves tetraspanin proteins and actin. In this study, we investigated the specific rol...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02906-12
更新日期:2013-03-01 00:00:00