Abstract:
:Artificial target sequences for tissue-specific miRNAs have recently been introduced as a new means for altering the tissue tropism of viral replication. This approach can be used to improve the safety of oncolytic viruses for cancer virotherapy by restricting their replication in unwanted tissues, such as the liver. Semliki Forest virus (SFV) is a positive-strand RNA virus and, similar to the related alphaviruses, like Sindbis virus, has potential as a gene therapy vector and an oncolytic virotherapy agent, but this potential is limited by the neurovirulence of these alphaviruses. Here, we have generated a replicative SFV4 carrying six tandem targets for the neuron-specific miR124 between the viral nonstructural protein 3 and 4 (nsp3 and nsp4) genes. When administered intraperitoneally into adult BALB/c mice, SFV4-miRT124 displayed an attenuated spread into the central nervous system (CNS) and greatly increased survival. Peripheral replication was not affected, indicating neuron-specific attenuation. Moreover, a strong protective SFV immunity was elicited in these animals. Intracranial infection of adult mice with SFV4-miRT124 showed greatly reduced infection of neurons in the brain but led to the infection of oligodendrocytes in the corpus callosum. Taken together, our data show that miR124-mediated attenuation of neurovirulence is a feasible and promising strategy for generating safer oncolytic alphavirus virotherapy agents.
journal_name
J Viroljournal_title
Journal of virologyauthors
Ylösmäki E,Martikainen M,Hinkkanen A,Saksela Kdoi
10.1128/JVI.01940-12subject
Has Abstractpub_date
2013-01-01 00:00:00pages
335-44issue
1eissn
0022-538Xissn
1098-5514pii
JVI.01940-12journal_volume
87pub_type
杂志文章abstract::Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominant Mamu-A(*)01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of S...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.23.12572-12578.2003
更新日期:2003-12-01 00:00:00
abstract:UNLABELLED:Generalized immune activation during HIV infection is associated with an increased risk of cardiovascular disease, neurocognitive disease, osteoporosis, metabolic disorders, and physical frailty. The mechanisms driving this immune activation are poorly understood, particularly for individuals effectively tre...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01257-14
更新日期:2014-08-01 00:00:00
abstract:UNLABELLED:Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent for Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a subset of multicentric Castleman disease (MCD). The KSHV life cycle has two principal gene repertoires, latent and lytic. KSHV viral interleukin-6 (vIL-6), an analog of human ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01192-15
更新日期:2015-10-21 00:00:00
abstract:UNLABELLED:Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replica...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01024-15
更新日期:2015-10-01 00:00:00
abstract:UNLABELLED:Equine influenza viruses (EIV) are responsible for rapidly spreading outbreaks of respiratory disease in horses. Although natural infections of humans with EIV have not been reported, experimental inoculation of humans with these viruses can lead to a productive infection and elicit a neutralizing antibody r...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02449-14
更新日期:2015-02-01 00:00:00
abstract::The E6 oncoproteins encoded by the cancer-associated human papillomaviruses (HPVs) can associate with and promote the degradation of wild-type p53 in vitro. To gain further insight into this process, the ability of HPV-16 E6 to complex with and promote the degradation of mutant forms of p53 was studied. A correlation ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.8.5100-5105.1992
更新日期:1992-08-01 00:00:00
abstract::HBI is a recombinant avian retrovirus with novel pathogenic properties that was derived from the myc-containing virus MC29. In contrast to MC29, which causes endotheliomas in chickens, HBI induces lymphoid tumors. The results of molecular cloning and nucleotide sequencing of HBI reported here show that the virus conta...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.3.969-977.1985
更新日期:1985-12-01 00:00:00
abstract::Human cytomegalovirus (CMV) is the leading cause of prenatal viral infection. Affected infants may suffer intrauterine growth retardation and serious neurologic impairment. Analysis of spontaneously aborted conceptuses shows that CMV infects the placenta before the embryo or fetus. In the human hemochorial placenta, m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.15.6808-6820.2000
更新日期:2000-08-01 00:00:00
abstract::In varicella-zoster virus (VZV)-infected primary human brain vascular adventitial fibroblasts (BRAFs), levels of beta interferon (IFN-β,) STAT1, and STAT2 transcripts as well as STAT1 and STAT2 protein were decreased. IFN-α transcript levels were increased but not secreted IFN-α protein levels. Compared to IFN-α-treat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01945-14
更新日期:2014-10-01 00:00:00
abstract::The production and selection of infectious vaccinia virus recombinants expressing foreign genes was facilitated by the construction of plasmid vectors. These vectors contain all or part of the vaccinia virus thymidine kinase (TK) gene interrupted by multiple unique restriction endonuclease sites placed adjacent to the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.3.857-864.1984
更新日期:1984-03-01 00:00:00
abstract::The herpes simplex virus glycoprotein designated VP7(B2) is extracted from virions by nonionic detergent in the form of an oligomer, whereas the other detergent-soluble envelope proteins appear to be extracted as monomers. The subunits of the VP7(B2) oligomer cannot be dissociated by 2-mercaptoethanol and are also res...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.3.1159-1167.1979
更新日期:1979-03-01 00:00:00
abstract::Two essential gene products of herpes simplex virus type 1, the viral DNA polymerase (pol) and UL42, its accessory protein, physically and functionally interact to form the core of the viral DNA replication complex. Understanding this essential interaction would provide a basis from which to develop novel anti-herpesv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.10.5922-5931.1993
更新日期:1993-10-01 00:00:00
abstract::Several C/EBP binding sites within the Rous sarcoma virus (RSV) long terminal repeat (LTR) and gag enhancers were mutated, and the effect of these mutations on viral gene expression was assessed. Minimal site-specific mutations in each of three adjacent C/EBP binding sites in the LTR reduced steady-state viral RNA lev...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.5.2862-2870.1993
更新日期:1993-05-01 00:00:00
abstract::A new method was developed for isolation of intracellular forms of simian virus 40 (SV40) nucleoprotein complexes from SV40-infected CV-1 cells late in the infectious cycle. In contrast to the Triton extraction method, which yields only a 60-70S complex, this new procedure yielded three forms of SV40 nucleoprotein com...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.2.612-623.1979
更新日期:1979-02-01 00:00:00
abstract::Retroviruses, as a result of the presence of two identical genomic RNA molecules in their virions, recombine at a high rate. When nonhomologous RNA is present in the dimer RNA molecules, nonhomologous recombination can occur, although the rate is very low, only 0.1% of the rate of essentially homologous recombination ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2409-2414.1994
更新日期:1994-04-01 00:00:00
abstract::Cytotoxic T lymphocytes (CTLs) play an important role in the immune response against respiratory syncytial virus (RSV) infection. The cell surface molecule lymphocyte function-associated antigen 1 (LFA-1) is an important contributor to CTL activation, CTL-mediated direct cell lysis, and lymphocyte migration. In an att...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.78.6.3014-3023.2004
更新日期:2004-03-01 00:00:00
abstract::We have used an antisense RNA approach in the analysis of gene function in human cytomegalovirus (HCMV). An astrocytoma cell line (U373-MG) that is permissive for virus replication was permanently transfected with a construct bearing sequence from HCMV UL44 (coding for the major late DNA-binding protein, ppUL44, also ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.4.2047-2057.1995
更新日期:1995-04-01 00:00:00
abstract::The human T-cell leukemia virus type 1 (HTLV-1) envelope protein is required for virus spread. This study further characterizes the role of the envelope protein in HTLV-1 immortalization. Viruses with single amino acid substitutions within the SU protein at residue 75, 81, 95, 101, 105, or 195 or with a C-terminal cyt...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.19.9553-9559.2001
更新日期:2001-10-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) does not replicate in murine cells. We investigated the basis of this block by infecting a murine NIH 3T3 reporter cell line that stably expressed human CD4, CCR5, and cyclin T1 and contained a transactivatable HIV-1 long terminal repeat (LTR)-green fluorescent protein (GFP)...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.8.3859-3870.2000
更新日期:2000-04-01 00:00:00
abstract::A rapid assay for retroviral reverse transcriptase activity released into the culture medium by infected cells was developed. With the assay, 4,000 clonally infected cell lines could be tested in a few hours. We have adapted the assay for use as a screen for the detection of spontaneous viral mutants. Mutants of Molon...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.38.1.239-248.1981
更新日期:1981-04-01 00:00:00
abstract::Understanding the microbiome of ticks in Australia is of considerable interest given the ongoing debate over whether Lyme disease and its causative agent, the bacterium Borrelia burgdorferisensu lato, are present in Australia. The diversity of bacteria infecting Australian ticks has been studied using both culture- an...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01358-18
更新日期:2019-01-17 00:00:00
abstract::The reasons for poor CD4+ T-cell recovery in some human immunodeficiency virus (HIV)-infected subjects despite effective highly active antiretroviral therapy (HAART) remain unclear. We recently reported that CXCR4-using (X4) HIV-1 could be gradually selected in cellular reservoirs during sustained HAART. Because of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00965-06
更新日期:2006-10-01 00:00:00
abstract::Stress signaling from mitochondria and the endoplasmic reticulum (ER) leads to the induction of the proapoptotic transcription factor CHOP/GADD153. Many viruses use the ER as a site of replication and/or envelopment, and this activity can lead to the activation of ER stress and apoptosis. African swine fever virus (AS...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.19.10825-10828.2004
更新日期:2004-10-01 00:00:00
abstract::Higher-order RNA structures in the 3' untranslated region (3'UTR) of enteroviruses are thought to play a pivotal role in viral negative-strand RNA synthesis. The structure of the 3'UTR was predicted by thermodynamic calculations using the STAR (structural analysis of RNA) computer program and experimentally verified u...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.1.686-696.1997
更新日期:1997-01-01 00:00:00
abstract::The discovery that hepatitis B virus (HBV) integrates into host chromosomes raises the question of whether such viral DNA integration correlates directly with the activation of specific oncogenes or the inactivation of anti-oncogenes. To obtain insight into this problem, we randomly collected HBV integrant samples fro...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.12.6761-6764.1991
更新日期:1991-12-01 00:00:00
abstract::A human cytomegalovirus (CMV) UL54 pol exonuclease domain II mutation, D413A, found in a clinical specimen, conferred ganciclovir (GCV) and cidofovir resistance but not foscarnet resistance when incorporated into laboratory strain T2294. After several passages without drug, mutation was observed in five of eight plaqu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01787-07
更新日期:2008-01-01 00:00:00
abstract:UNLABELLED:JC polyomavirus (JCPyV) infection of immunocompromised individuals results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). The viral capsid of JCPyV is composed primarily of the major capsid protein virus protein 1 (VP1), and pentameric arrangement of VP1 monomers results...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00089-15
更新日期:2015-04-01 00:00:00
abstract::Two mutant strains (vi12 and vi13) of herpes simplex virus that contain insertion mutations in the sequences that encode the DNA-binding domain of viral regulatory protein ICP4 were generated. Both mutations disrupted specific DNA binding and resulted in transcriptionally inactive molecules; however, the ability of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.1.299-307.1991
更新日期:1991-01-01 00:00:00
abstract::A detailed restriction endonuclease map for the genome of Bacillus subtilis phage SP01 is presented. Sites of cleavage for the restriction enzymes BglII, EcoRI, HaeIII, and SalI were determined. This physical map showed that SP01 DNA was 140 kilobases in length and contained a repeated sequence of 12.4 kilobases at it...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.31.1.156-171.1979
更新日期:1979-07-01 00:00:00
abstract::We previously observed that when human immunodeficiency virus (HIV)-infected T lymphocytes are added to epithelial cells, they adhere, polarize, and secrete virions unidirectionally onto the epithelium. Epithelial cells subsequently take up virus and become productively infected. We report here that colchicine treatme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.5.2898-2905.1994
更新日期:1994-05-01 00:00:00