Abstract:
UNLABELLED:Translation machinery is a major recipient of the principal mitogenic signaling networks involving Raf-ERK1/2 and phosphoinositol 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR). Picornavirus internal ribosomal entry site (IRES)-mediated translation and cytopathogenic effects are susceptible to the status of such signaling cascades in host cells. We determined that tumor-specific cytotoxicity of the poliovirus/rhinovirus chimera PVSRIPO is facilitated by Raf-ERK1/2 signals to the mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) and its effects on the partitioning/activity of the Ser/Arg (SR)-rich protein kinase (SRPK) (M. C. Brown, J. D. Bryant, E. Y. Dobrikova, M. Shveygert, S. S. Bradrick, V. Chandramohan, D. D. Bigner, and M, Gromeier, J. Virol. 22:13135-13148, 2014, doi:http://dx.doi.org/10.1128/JVI.01883-14). Here, we show that MNK regulates SRPK via mTOR and AKT. Our investigations revealed a MNK-controlled mechanism acting on mTORC2-AKT. The resulting suppression of AKT signaling attenuates SRPK activity to enhance picornavirus type 1 IRES translation and favor PVSRIPO tumor cell toxicity and killing. IMPORTANCE:Oncolytic immunotherapy with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES, is demonstrating early promise in clinical trials with intratumoral infusion in recurrent glioblastoma (GBM). Our investigations demonstrate that the core mechanistic principle of PVSRIPO, tumor-selective translation and cytotoxicity, relies on constitutive ERK1/2-MNK signals that counteract the deleterious effects of runaway AKT-SRPK activity in malignancy.
journal_name
J Viroljournal_title
Journal of virologyauthors
Brown MC,Dobrikov MI,Gromeier Mdoi
10.1128/JVI.01884-14subject
Has Abstractpub_date
2014-11-01 00:00:00pages
13149-60issue
22eissn
0022-538Xissn
1098-5514pii
JVI.01884-14journal_volume
88pub_type
杂志文章abstract::We have constructed two point mutants of Rous sarcoma virus in which the amino-terminal glycine residue of the transforming protein, p60src, was changed to an alanine or a glutamic acid residue. Both mutant proteins failed to become myristylated and, more importantly, no longer transformed cells. The lack of transform...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.58.2.468-474.1986
更新日期:1986-05-01 00:00:00
abstract::The structures of canine parvovirus (CPV) and feline parvovirus (FPV) complexed with antibody fragments from eight different neutralizing monoclonal antibodies were determined by cryo-electron microscopy (cryoEM) reconstruction to resolutions varying from 8.5 to 18 A. The crystal structure of one of the Fab molecules ...
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doi:10.1128/JVI.02532-08
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00120-13
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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
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abstract::High concentrations of either trypsin or chymotrypsin caused nearly complete cleavage of capsid protein VP2 of hepatitis A virus but did not significantly reduce the infectivity, thermostability, or antigenicity of the virus. Chymotrypsin also had a lesser effect on VP1. These findings indicate the presence of a prote...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5636-5640.1991
更新日期:1991-10-01 00:00:00
abstract::Foxp3(+) CD4(+) regulatory T cells (Tregs) represent a highly suppressive T cell subset with well-characterized immunosuppressive effects during immune homeostasis and chronic infections, although the role of these cells in acute viral infections is poorly understood. The present study sought to examine the induction ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.05685-11
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abstract::The duck hepatitis B virus (DHBV) pregenomic RNA is a bicistronic mRNA encoding the core and polymerase proteins. Thirteen AUGs (C2 to C14) and 10 stop codons (S1 to S10) are located between the C1 AUG for the core protein and the P1 AUG that initiates polymerase translation. We previously found that the translation o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01263-08
更新日期:2009-02-01 00:00:00
abstract::To model human immunodeficiency virus (HIV) perinatal transmission, we studied infection of simian-human immunodeficiency virus (SHIV) SF162P3 in 10 pregnant Macaca nemestrina females and their offspring. Four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95...
journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00438-12
更新日期:2012-11-01 00:00:00
abstract::It is shown that gene 5 protein of bacteriophage M13 is one of the major proteins synthesized in vitro under the direction of M13 replicative-form DNA. By means of DNA-cellulose chromatography, this protein has been purified to homogeneity and its biological characteristics have been compared with those of its native ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.6.1466-1472.1973
更新日期:1973-12-01 00:00:00
abstract::Determinants of glycosylation site usage were explored by using the hemagglutinin-neuraminidase (HN) glycoprotein of the paramyxovirus Newcastle disease virus. The amino acid sequence of the HN protein, a type II glycoprotein, has six N-linked glycosylation addition sites, G1 to G6, two of which, G5 and G6, are not us...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.4.3083-3089.1997
更新日期:1997-04-01 00:00:00
abstract::Analyses, by construction of phage growth curves, indicated that the polysaccharide depolymerase was synthesized by Pseudomonas aeruginosa strains B and BI after infection with phage 2. The kinetics of biosynthesis of the depolymerase were found to parallel closely the rate of formation of phage-directed virions, and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.3.3.290-296.1969
更新日期:1969-03-01 00:00:00
abstract::In an effort to identify host proteins involved in herpes simplex virus type 1 replication, monkey and human cellular protein activities (called OF-1) that bind the viral replication origin, oriS, have been described. We show by mass spectrometry that the DNA-binding component of human OF-1 contains Ku70 and Ku80 prot...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.14.7839-7842.2004
更新日期:2004-07-01 00:00:00
abstract::The Aichi virus 2A protein is not a protease, unlike many other picornavirus 2A proteins, and it is related to a cellular protein, H-rev107. Here, we examined the replication properties of two 2A mutants in Vero cells and a cell-free translation/replication system. In one mutant, amino acids 36 to 126 were replaced wi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01051-08
更新日期:2008-10-01 00:00:00
abstract::Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations requi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.24.13819-13828.2004
更新日期:2004-12-01 00:00:00
abstract::Friend murine spleen focus-forming virus (SFFV) encodes a glycoprotein designated gp52, which is responsible for the leukemogenic properties of the virus. gp52 lacks a cytoplasmic domain and is defective in its transport to the cell surface. We constructed a chimeric envelope gene which codes for a molecule with an ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.12.4007-4011.1987
更新日期:1987-12-01 00:00:00
abstract::Injection of conventional or axenic weanling mice with potent sheep or goat antibody to mouse interferon alpha/beta resulted in a decrease in the basal level of 2-5A synthetase in resting peritoneal macrophages and rendered these cells permissive for vesicular stomatitis virus. There was a good inverse correlation bet...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.53.1.221-227.1985
更新日期:1985-01-01 00:00:00
abstract::The cell culture lines HTG2 and HTG3 were established from a transplantable hamster tumor induced by a murine sarcoma virus (strain Gz-MSV) after 17 and 60 in vivo passages, respectively. The viruses released by these two cell lines markedly differ in morphology, antigenic composition, infectivity, transforming abilit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.12.4.931-936.1973
更新日期:1973-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.61.9.2670-2674.1987
更新日期:1987-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.5.646-650.1971
更新日期:1971-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.378-382.1997
更新日期:1997-01-01 00:00:00
abstract::Synthetic peptides of increasing length and corresponding in sequence to the C-terminal end of the HA1 molecule of influenza virus were constructed and examined for their immunogenic and antigenic properties. Peptides containing at least the four C-terminal amino acids, when coupled to keyhole limpet hemocyanin, were ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.62.12.4745-4751.1988
更新日期:1988-12-01 00:00:00
abstract::Bacteriophage PRD1 contains DNA, 17 proteins, and lipid. The assembly pathway involves the formation of empty particles that contain lipid and all of the proteins of mature virions, with the possible exception of one. The major and minor capsid proteins, P3 and P5, occur as soluble multimers before they appear in the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.44.3.1021-1030.1982
更新日期:1982-12-01 00:00:00
abstract::Genetic and phylogenetic analyses suggest that the pandemic H1N1/2009 virus was derived from well-established swine influenza lineages; however, there is no convincing evidence that the pandemic virus was generated from a direct precursor in pigs. Furthermore, the evolutionary dynamics of influenza virus in pigs have ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01679-14
更新日期:2014-10-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) mutants with codon insertions and deletions in IE-0, the gene encoding ICP0, were constructed. The HSV-1 deletion mutant dl1403 (N. D. Stow and E. C. Stow, J. Gen. Virol. 67:2571-2585, 1986) and an IE-0:lacZ transplacement vector isolated in this study were used to facilitate the co...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.5.2916-2927.1992
更新日期:1992-05-01 00:00:00
abstract::Productive infection by the murine autonomous parvovirus minute virus of mice (MVM) depends on a dividing cell population and its differentiation state. We have extended the in vivo analysis of the MVM host cell type range into the developing embryo by in utero inoculation followed by further gestation. The fibrotropi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.17.9474-9486.2004
更新日期:2004-09-01 00:00:00
abstract::Our previous observations indicated that upon infection with minute virus of mice (MVM), Ehrlich ascites cells lose a transcription elongation activity which is essential for the readthrough of the MVM attenuator. This was monitored by the ability of extracts from uninfected but not from infected cells to support read...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2741-2745.1994
更新日期:1994-04-01 00:00:00
abstract::All presently available replication-competent proviral clones of human immunodeficiency virus type 1 (HIV-1) are derived from cell culture-amplified virus. Since tissue culture is highly selective for viral strains with an in vitro growth advantage, such clones may not be representative of the biologically relevant vi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.8.3973-3985.1991
更新日期:1991-08-01 00:00:00
abstract::A protein-protein interaction within the helicase domain of the Tobacco mosaic virus (TMV) 126- and 183-kDa replicase proteins was previously implicated in virus replication (S. Goregaoker, D. Lewandowski, and J. Culver, Virology 282:320-328, 2001). To further characterize the interaction, polypeptides covering the in...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.6.3549-3556.2003
更新日期:2003-03-01 00:00:00