Abstract:
:Viral fusogenic membrane proteins have been proposed as tools to increase the potency of oncolytic viruses, but there is a need for mechanisms to control the spread of fusogenic viruses in normal versus tumor cells. We have previously shown that a mutant of the paramyxovirus simian virus 5 (SV5) that harbors mutations in the P/V gene from the canine parainfluenza virus (P/V-CPI(-)) is a potent inducer of type I interferon (IFN) and apoptosis and is restricted for spread through normal but not tumor cells in vitro. Here, we have used the cytopathic P/V-CPI(-) as a backbone vector to test the hypothesis that a virus expressing a hyperfusogenic glycoprotein will be a more effective oncolytic vector but will retain sensitivity to IFN. A P/V mutant virus expressing an F protein with a glycine-to-alanine substitution in the fusion peptide (P/V-CPI(-)-G3A) was more fusogenic than the parental P/V-CPI(-) mutant. In two model prostate tumor cell lines which are defective in IFN production (LNCaP and DU145), the hyperfusogenic P/V-CPI(-)-G3A mutant had normal growth properties at low multiplicities of infection and was more effective than the parental P/V-CPI(-) mutant at cell killing in vitro. However, in PC3 cells which produce and respond to IFN, the hyperfusogenic P/V-CPI(-)-G3A mutant was attenuated for growth and spread. Killing of PC3 cells was equivalent between the parental P/V-CPI(-) mutant and the hyperfusogenic P/V-CPI(-)-G3A mutant. In a nude mouse model using LNCaP cells, the hyperfusogenic P/V-CPI(-)-G3A mutant was more effective than P/V-CPI(-) at reducing tumor burden. In the case of DU145 tumors, the two vectors based on P/V-CPI(-) were equally effective at limiting tumor growth. Together, our results provide proof of principle that a cytopathic SV5 P/V mutant can serve as an oncolytic virus and that the oncolytic effectiveness of P/V mutants can be enhanced by a fusogenic membrane protein without compromising sensitivity to IFN. The potential advantages of SV5-based oncolytic vectors are discussed.
journal_name
J Viroljournal_title
Journal of virologyauthors
Gainey MD,Manuse MJ,Parks GDdoi
10.1128/JVI.01054-08subject
Has Abstractpub_date
2008-10-01 00:00:00pages
9369-80issue
19eissn
0022-538Xissn
1098-5514pii
JVI.01054-08journal_volume
82pub_type
杂志文章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:UNLABELLED:The majority of currently circulating influenza A(H1N1) viruses are antigenically similar to the virus that caused the 2009 influenza pandemic. However, antigenic variants are expected to emerge as population immunity increases. Amino acid substitutions in the hemagglutinin protein can result in escape from ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02962-14
更新日期:2015-04-01 00:00:00
abstract::Sindbis virus nonstructural polyproteins and their cleavage products are believed to be essential components of viral RNA replication and transcription complexes. Although numerous studies have investigated the effect of mutations in nsP1-, nsP2-, and nsP4-coding regions on Sindbis virus-specific RNA synthesis, relati...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.9.5781-5791.1994
更新日期:1994-09-01 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::The human herpes simplex virus (HSV) protein VP16 induces formation of a transcriptional regulatory complex with two cellular factors-the POU homeodomain transcription factor Oct-1 and the cell proliferation factor HCF-1-to activate viral immediate-early-gene transcription. Although the cellular role of Oct-1 in trans...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.24.12402-12411.2001
更新日期:2001-12-01 00:00:00
abstract::The protection of individuals from human immunodeficiency virus type 1 (HIV-1) infection with an envelope subunit derived from a single isolate will require the presentation of conserved epitopes in gp120. The objective of the studies presented here was to test whether a native recombinant gp120 (rgp120) immunogen wou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.1.172-182.1992
更新日期:1992-01-01 00:00:00
abstract::Alphaviruses represent a serious public health threat and cause a wide variety of diseases, ranging from severe encephalitis, which can result in death or neurological sequelae, to mild infection, characterized by fever, skin rashes, and arthritis. In the infected cells, alphaviruses express only four nonstructural pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01011-08
更新日期:2008-10-01 00:00:00
abstract::Shrimp subcuticular epithelial cells are the initial and major targets of white spot syndrome virus (WSSV) infection. Proteomic studies of WSSV-infected subcuticular epithelium of Penaeus monodon were performed through two approaches, namely, subcellular fractionation coupled with shotgun proteomics to identify viral ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01006-07
更新日期:2007-11-01 00:00:00
abstract::Anaplastic nasopharyngeal carcinoma (NPC) cells invariably harbor the Epstein-Barr virus (EBV) genome, an association that is unique among human virus-associated cancers. Although EBV is able to replicate in epithelial cells, results with expression of the EBV receptor (complement receptor type 2 [CR2]; also called CD...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.10.4121-4128.1989
更新日期:1989-10-01 00:00:00
abstract::The DNase/alkaline exonuclease (AE) genes are well conserved in all herpesvirus families, but recent studies have shown that the AE proteins of gammaherpesviruses such as Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) exhibit an additional function which shuts down host protein synthesis. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01946-07
更新日期:2008-03-01 00:00:00
abstract::Extracts from nodavirus-infected Drosophila cells contained detergent-labile 140S "young" particles much richer than mature virions in their content of protein alpha, a precursor of coat proteins beta and gamma. Incorporation studies in infected cells showed that most newly synthesized alpha protein was assembled into...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.9.3399-3406.1988
更新日期:1988-09-01 00:00:00
abstract::Subcutaneous injection of FK506 (10 mg/kg of body weight) completely blocked the clonal expansion of staphylococcal enterotoxin A (SEA)-reactive T cells in healthy (control) mice after SEA injection but did not disturb it in mice with murine AIDS (MAIDS) caused by infection with LP-BM5 murine leukemia virus. MAIDS mic...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.746-749.1997
更新日期:1997-01-01 00:00:00
abstract::Based on previous structural and functional studies, a potential receptor-binding site composed of residues that form a pocket at one end of the two long antiparallel helices in the receptor-binding domain of Friend 57 murine leukemia virus envelope protein (RBD) has been proposed. To test this hypothesis, directed su...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.5.3758-3763.1999
更新日期:1999-05-01 00:00:00
abstract::Using coimmunoprecipitation and glutathione S-transferase pulldown experiments, we found that polyomavirus large T antigen binds to p300 in vivo and in vitro. The N-terminal region of the viral protein, including the pRB binding motif, was dispensable for this interaction, which involved several regions within the C-t...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.2.1734-1739.1999
更新日期:1999-02-01 00:00:00
abstract::Theiler murine encephalomyelitis virus (TMEV) infection of a mouse's central nervous system is biphasic: first the virus infects motor neurons (acute phase), and this is followed by a chronic phase in which the virus infects glial cells (primarily microglia and macrophages [M]) of the spinal cord white matter, leading...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03395-12
更新日期:2013-04-01 00:00:00
abstract::Mengovirus 14S subviral protein particles generated in infected L cells and in a cell-free translation system primed with mengovirus RNA were purified by sucrose gradient centrifugation and immunoaffinity chromatography. The preparations from both sources contained essentially pure proteins epsilon, alpha, and gamma, ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.57.1.275-284.1986
更新日期:1986-01-01 00:00:00
abstract::Vaccinia virus DNA fragments that have been denatured by alkali and then neutralized contain a fraction that rapidly reforms duplex structures. The fraction is enriched by fractionating on hydroxyapatite columns and serves as as substrate for digestion by two restriction endonucleases isolated from Hemophilus parainfl...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.17.1.227-238.1976
更新日期:1975-01-01 00:00:00
abstract::Herpes simplex virus 1 (HSV-1) and HSV-2 are large, double-stranded DNA viruses that cause lifelong persistent infections characterized by periods of quiescence and recurrent disease. How HSV evolves within an infected individual experiencing multiple episodes of recurrent disease over time is not known. We determined...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00942-17
更新日期:2017-11-14 00:00:00
abstract::Herpes simplex virus (HSV) codes for several envelope glycoproteins, including glycoprotein G-2 (gG-2) of HSV type 2 (HSV-2), which are dispensable for replication in cell culture. However, clinical isolates which are deficient in such proteins occur rarely. We describe here five clinical HSV-2 isolates which were fou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.12.9796-9802.1999
更新日期:1999-12-01 00:00:00
abstract:UNLABELLED:CBFβ was recently found to be a key regulator of the ability of human immunodeficiency virus type 1 (HIV-1) Vif to overcome host antiviral APOBEC3 proteins. However, the detailed molecular requirements for the Vif-CBFβ interaction are still not clear. Here, we mapped the minimum Vif domain required for CBFβ ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03604-13
更新日期:2014-03-01 00:00:00
abstract::The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cyste...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4546-4550.1992
更新日期:1992-07-01 00:00:00
abstract::The purpose of this study was to determine whether a cell surface protein that can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry, herpesvirus entry mediator (previously designated HVEM but renamed HveA), also mediates HSV-1-induced cell-cell fusion. We found that transfection of DNA from KOS-804, a...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.7.5802-5810.1998
更新日期:1998-07-01 00:00:00
abstract::We reported previously that an N-terminally truncated insulinlike growth factor I receptor (IGFR) fused to avian sarcoma virus UR2 gag p19 had a greater transforming potential than did the native IGFR, but it failed to cause tumors in vivo. To investigate whether the 36 amino acids (aa) of the IGFR extracellular (EC) ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.1.9-18.1993
更新日期:1993-01-01 00:00:00
abstract::Viral RNA-dependent RNA polymerases exhibit great sequence diversity. Only six core amino acids are conserved across all polymerases of positive-strand RNA viruses of eukaryotes. While exploring the function of one of these completely conserved residues, asparagine 297 in the prototypic poliovirus polymerase 3D(pol), ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.9.5378-5388.2003
更新日期:2003-05-01 00:00:00
abstract:UNLABELLED:PD-1 is an inhibitory receptor that has a major role in T cell dysfunction during chronic infections and cancer. While demethylation of the PD-1 promoter DNA is observed in exhausted T cells isolated from chronically infected individuals, little is known about when this stable demethylation of PD-1 promoter ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00798-16
更新日期:2016-09-12 00:00:00
abstract::Genetic and biochemical studies have suggested the existence of a bacteriophage-like, DNA-packaging/ejecting portal complex in herpesviruses capsids, but its arrangement remained unknown. Here, we report the first visualization of a unique vertex in the Kaposi's sarcoma-associated herpesvirus (KSHV) capsid by cryoelec...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02254-06
更新日期:2007-04-01 00:00:00
abstract::The v-src coding region was deleted from cloned Rous sarcoma virus DNA, and the deleted clones were tested for infectivity by transfection. All of the coding region, as well as most of the sequences lying between v-src and the unique 3' region (U3), could be deleted without affecting viability. However, at least 9 and...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.43.2.482-488.1982
更新日期:1982-08-01 00:00:00
abstract::The great majority of viral mRNAs in mouse C127 cells transformed by bovine papillomavirus type 1 (BPV) have a common 3' end at the early polyadenylation site which is 23 nucleotides (nt) downstream of a canonical poly(A) consensus signal. Twenty percent of BPV mRNA from productively infected cells bypasses the early ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.12.7705-7710.1993
更新日期:1993-12-01 00:00:00
abstract::The bovine papillomavirus E5 gene encodes a 44-amino-acid, homodimeric transmembrane protein that is the smallest known transforming protein. The E5 protein transforms cultured fibroblasts by forming a stable complex with the endogenous platelet-derived growth factor (PDGF) beta receptor through transmembrane and juxt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.73.4.3264-3272.1999
更新日期:1999-04-01 00:00:00
abstract::BALB/c mice infected on the scarified cornea with herpes simplex virus type 1 strain 35 [HSV-1(35)] rarely developed ocular disease even at challenge doses as high as 10(7) PFU per eye. In contrast, HSV-1(RE) consistently induced stromal keratitis at an inoculum of 2 x 10(4) PFU. The goal of this study was to determin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.5.2187-2192.1990
更新日期:1990-05-01 00:00:00