Abstract:
:In our search for novel inhibitors of herpes simplex virus type 1 (HSV-1), a new class of thiourea inhibitors was discovered. N-(4-[3-(5-Chloro-2,4-dimethoxyphenyl)-thioureido]-phenyl)-acetamide and its 2-fluoro-benzamide derivative inhibited HSV-1 replication. HSV-2, human cytomegalovirus, and varicella-zoster virus were inhibited to a lesser extent. The compounds acted late in the replication cycle by impairing both the cleavage of concatameric viral DNA into progeny genome length and the packaging of the DNA into capsids, indicative of a defect in the encapsidation process. To uncover the molecular target of the inhibition, resistant HSV-1 isolates were generated, and the mutation responsible for the resistance was mapped using marker transfer techniques. Each of three independent isolates had point mutations in the UL6 gene which resulted in independent single-amino-acid changes. One mutation was located in the N terminus of the protein (E121D), while two were located close together in the C terminus (A618V and Q621R). Each of these point mutations was sufficient to confer drug resistance when introduced into wild-type virus. The UL6 gene is one of the seven HSV-1 genes known to play a role in DNA packaging. This novel class of inhibitors has provided a new tool for dissection of HSV-1 encapsidation mechanisms and has uncovered a new viable target for the treatment of herpesviral diseases.
journal_name
J Viroljournal_title
Journal of virologyauthors
van Zeijl M,Fairhurst J,Jones TR,Vernon SK,Morin J,LaRocque J,Feld B,O'Hara B,Bloom JD,Johann SVdoi
10.1128/jvi.74.19.9054-9061.2000subject
Has Abstractpub_date
2000-10-01 00:00:00pages
9054-61issue
19eissn
0022-538Xissn
1098-5514journal_volume
74pub_type
杂志文章abstract:UNLABELLED:Epstein-Barr virus (EBV) is a well-established B-cell-tropic virus associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV is associated with a number of T-cell lymphomas; however, in vitro studies utilizing prototypical EBV type 1 (EBV-1) laboratory strains have genera...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03001-14
更新日期:2015-02-01 00:00:00
abstract::Mechanisms by which the plus-sense RNA genomes of picornaviruses are replicated remain poorly defined, but existing models do not suggest a role for sequences encoding the capsid proteins. However, candidate RNA replicons (delta P1 beta gal and delta P1Luc), representing the sequence of human rhinovirus 14 virus (HRV-...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.1941-1952.1996
更新日期:1996-03-01 00:00:00
abstract::Sequencing and reversion analysis of murine hepatitis virus (MHV) temperature-sensitive (ts) viruses has identified putative ts mutations in the replicase nonstructural proteins (nsp's) of these coronaviruses. In this study, reverse transcriptase PCR sequencing of the RNA genome of an isolate of the MHV ts virus Alb t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00203-08
更新日期:2008-06-01 00:00:00
abstract::Treatment with sodium dodecyl sulfate (SDS) converted the vaccinia virus strain IHD-J into particles of two types: (i) ghosts which possessed a thin-membrane vesicle derived from basement part of the virus membrane with attached lateral bodies and a membranous structure derived from the core wall and (ii) aggregates o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.50.3.929-938.1984
更新日期:1984-06-01 00:00:00
abstract::Nucleotide sequence analysis of two simian virus 40 early mutants dl1263 and dl1265, which lack a DNA segment around map positions 0.21 and 0.18, respectively (C. Cole, T. Landers, S. Goff, S. MAnteuil-Brutlag, and P. Berg, J. Virol. 24:277--294, 1977), revealed in-phase deletions of 33 nucleotide pairs for dl1263 and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.30.3.936-941.1979
更新日期:1979-06-01 00:00:00
abstract::Human T-cell lymphotropic virus type 1 (HTLV-1) is transmitted through a viral synapse and enters target cells via interaction with the glucose transporter GLUT1. Here, we show that Neuropilin-1 (NRP1), the receptor for semaphorin-3A and VEGF-A165 and a member of the immune synapse, is also a physical and functional p...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02719-05
更新日期:2006-07-01 00:00:00
abstract::3-O-(3',3'-Dimethysuccinyl) betulinic acid (PA-457) has been shown to potently inhibit human immunodeficiency virus (HIV) replication in culture. In contrast to inhibitors that act upon the viral proteinase, PA-457 appears to block only the final maturational cleavage of p25CA-p2 to p24CA. However, attempts to replica...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02743-05
更新日期:2006-06-01 00:00:00
abstract::Cervical cancer develops through the combined activities of the human papillomavirus (HPV) E6 and E7 oncoproteins. A defining characteristic of E6 oncoproteins derived from cancer-causing HPV types is the presence of a PDZ binding motif (PBM) at the extreme carboxy terminus of the protein which is absent from E6 prote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02074-12
更新日期:2013-02-01 00:00:00
abstract::The morphology of Safferman's virus of blue-green algae (phycovirus LPP-1) has been studied by electron microscopy and physicochemical methods. The virion has a short (100 to 200 A long, 150 A in diameter) forked tail, with an outer sheath, an inner core, and a capital attached to one of the vertices of a polyhedral h...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.1.2.344-361.1967
更新日期:1967-04-01 00:00:00
abstract::The roles of intracellular naked (INV), cell-associated enveloped (CEV), and extracellular enveloped (EEV) forms of vaccinia virus in cell-to-cell and longer-range spread were investigated by using two closely related strains of vaccinia virus, WR and IHD-J. We confirmed previous results that WR and IHD-J produced sim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4170-4179.1992
更新日期:1992-07-01 00:00:00
abstract::The effect of bacteriophage SPO1 infection of Bacillus subtilis and a deoxyribonucleic acid (DNA) polymerase-deficient (pol(-)) mutant of this microorganism on the synthesis of DNA has been examined. Soon after infection, the incorporation of deoxyribonucleoside triphosphates into acid-insoluble material by cell lysat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.9.2.263-272.1972
更新日期:1972-02-01 00:00:00
abstract::Human T-cell leukemia virus type 1 (HTLV-1) remains latent throughout the life of the carrier, with cells containing the provirus and viral gene expression efficiently down-regulated. On a molecular level, exactly how viruses are down-regulated in vivo remains unresolved. We described here the possibility that down-re...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.6.4485-4494.1997
更新日期:1997-06-01 00:00:00
abstract:UNLABELLED:Following retrovirus entry, the viral capsid (CA) disassembles into its component capsid proteins. The rate of this uncoating process, which is regulated by CA-CA interactions and by the association of the capsid with host cell factors like cyclophilin A (CypA), can influence the efficiency of reverse transc...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01388-14
更新日期:2014-09-01 00:00:00
abstract::The humoral immune response of cats that were naturally infected with the feline leukemia virus (FeLV) was examined after antigenic stimulation with the synthetic antigen poly(L-Tyr, L-Glu)-poly(DL-Ala)-poly(L-Lys). The primary humoral antibody response in FeLV-infected cats was both delayed and greatly reduced, compa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.669-673.1986
更新日期:1986-11-01 00:00:00
abstract::Substitution of a methionine residue at position 79 in poliovirus protein 3A with valine or threonine caused defective viral RNA synthesis, manifested as delayed onset and reduced yield of viral RNA, in HeLa cells transfected with a luciferase-containing replicon. Viruses containing these same mutations produced small...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.23.12679-12691.2003
更新日期:2003-12-01 00:00:00
abstract::Protein kinase activity in general is stimulated at least 5- to 10-fold in ribosomal salt wash preparations from poliovirus-infected HeLa cells compared with those from mock-infected cells. The stimulation of kinase activity is manifested by increased phosphorylation of ribosome-associated polypeptides having approxim...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.6.1781-1787.1987
更新日期:1987-06-01 00:00:00
abstract::The human antibody response to flavivirus infection is dominantly directed against a cross-reactive epitope on the fusion loop of domain II (DII-FL) of the envelope (E) protein. Although antibodies against this epitope fail to recognize fully mature West Nile virus (WNV) virions and accordingly neutralize infection po...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05859-11
更新日期:2011-11-01 00:00:00
abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is a 1,162-amino-acid protein that mediates episome persistence of viral genomes. LANA binds the KSHV terminal-repeat (TR) sequence through its carboxy-terminal domain to mediate DNA replication. LANA simultaneously binds mitotic ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02158-18
更新日期:2019-03-05 00:00:00
abstract::Thirteen dengue virus-specific, cytotoxic CD4+ CD8- T-cell clones were established from a donor who was infected with dengue virus type 3. These clones were examined for virus specificity and human leukocyte antigen (HLA) restriction in cytotoxic assays. Six patterns of virus specificities were determined. Two serotyp...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.4.1823-1828.1991
更新日期:1991-04-01 00:00:00
abstract::During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma-/- mice previously immunized with the A/HK/68 (H3N2) ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.8.6637-6645.1998
更新日期:1998-08-01 00:00:00
abstract::In this study, we show that human cytomegalovirus DNA synthesis is inhibited in infected confluent human embryonic lung cells treated with the DNA-intercalative topoisomerase II inhibitor 4-9'-(acridinylamino)methanesulfon-m-anisidide (m-AMSA). Similar inhibitory effects were observed with VM-26, a nonintercalative to...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.12.4797-4800.1988
更新日期:1988-12-01 00:00:00
abstract::Integrin-using rotaviruses bind MA104 cell surface alpha2beta1 integrin via the Asp-Gly-Glu (DGE) sequence in virus spike protein VP4 and interact with alphaxbeta2 integrin during cell entry through outer capsid protein VP7. Infection is inhibited by the alpha2beta1 ligand Asp-Gly-Glu-Ala (DGEA) and the alphaxbeta2 li...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.21.11786-11797.2004
更新日期:2004-11-01 00:00:00
abstract::The genome of the Neodiprion sertifer nucleopolyhedrovirus (NeseNPV), which infects the European pine sawfly, N. sertifer (Hymenoptera: Diprionidae), was sequenced and analyzed. The genome was 86,462 bp in size. The C+G content of 34% was lower than that of the majority of baculoviruses. A total of 90 methionine-initi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.13.7036-7051.2004
更新日期:2004-07-01 00:00:00
abstract::The internal hydrophobic sequence within the flaviviral capsid protein (protein C) plays an important role in the assembly of infectious virions. Here, this sequence was analyzed in a West Nile virus lineage I isolate (crow V76/1). An infectious cDNA clone was constructed and used to introduce deletions into the inter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02653-08
更新日期:2009-06-01 00:00:00
abstract::The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2(b)-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed agains...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.7.5981-5993.1999
更新日期:1999-07-01 00:00:00
abstract::We isolated revertants of a polyomavirus whose origin of DNA replication contains a point mutation in the palindrome to which large T antigen binds. Four independent second-site revertants contain an Asp-286----Asn-286 substitution in large T antigen. This mutant large T antigen activates replication of DNAs containin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.1.242-249.1989
更新日期:1989-01-01 00:00:00
abstract::Growth of phage phi105 and its deoxyribonucleic acid (DNA) was studied in radiation-sensitive mutants of Bacillus subtilis. The recA gene is required for optimal prophage induction with mitomycin C and for infectivity of prophage DNA. rec B gene is required for marker rescue from mature DNA. The importance of bacteria...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.8.6.919-921.1971
更新日期:1971-12-01 00:00:00
abstract:UNLABELLED:Japanese encephalitis (JE) is an arthropod-borne disease associated with the majority of viral encephalitis cases in the Asia-Pacific region. The causative agent, Japanese encephalitis virus (JEV), has been phylogenetically divided into five genotypes. Recent surveillance data indicate that genotype I (GI) i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02050-14
更新日期:2014-10-01 00:00:00
abstract::Glycoprotein D (gD) of herpes simplex virus type 1 (HSV-1) was modified to encode targeting signals known to localize proteins to either the endoplasmic reticulum (ER) or the trans-Golgi network. These motifs conferred the predicted targeting properties on gD in transfected cells as judged by immunofluorescence staini...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.11.9515-9520.1999
更新日期:1999-11-01 00:00:00
abstract::The nef genes of the human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2) and the related simian immunodeficiency viruses (SIVs) encode a protein (Nef) whose role in virus replication and cytopathicity remains uncertain. As an attempt to elucidate the function of nef, we characterized the nucleotide and corre...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.8.4639-4650.1993
更新日期:1993-08-01 00:00:00